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momofthegoons

Vapor Accessory Addict
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Effects of Cannabis on the Central Nervous System

Effects of Cannabis
There have been many speculations about the effects that cannabis, or its active ingredient delta-9-tetrahydrocannabinol, has on the central nervous system (CNS). However, while THC may be the most active chemical substance in cannabis, there are over 400 different substances in cannabis. Of these, there are approximately 66 known cannabinoids that are found exclusively on the cannabis plant. While all of these bind to the cannabinoid receptors in the brain, THC is not only the cannabinoid that binds best to the receptor but it is also the natural component that is most effective medically.

The cannabinoid receptors are also activated by the endogenous cannabinoids naturally created in the body. In humans this neurotransmitter is known as anandamide (N-arachidonoylethanolamide or AEA). THC is the phytocannabinoid (not created naturally in the body) that mimics anandamide in the body. The cannabinoid receptors are a group of G-coupled protein receptor (seven-transmembrane domain receptors) which means that there are seven transmembrane alpha-helices that detect a cannabinoid on the outside of the membrane and immediately release factors on the inside of the nerve terminal. The receptors that the cannabinoid receptors activate are known at the CB1 and CB2 receptors. The cannabinoid receptors are the only two of their kind that are known to be located in cell membranes of mammals, birds, fish and reptiles.

CB1 receptors are predominantly found in the brain in the basal ganglia and the hippocampus. They are also found in the cerebellum, and the male and female reproductive organs. The CB1 receptor is associated with feelings of euphoria, and it also has plays a role in anticonvulsive pathways. The places where these receptors are absent are the medulla oblongata and the brain stem. The brainstem and medulla oblongata are responsible for cardiovascular and respiratory functions; not having the cannabinoid receptor would leave them completely unaffected by THC, or any other cannabinoid. The lack of cannabinoid receptors on the medulla also might suggest why there has never been a case of overdose of THC, reguardless of the amount consumed or the method of consumption. Likewise, there is a lack of cannabinoid receptors on the mesocorticolimbic pathway means that there is a significantly decreased chance of physical addiction because a dopaminergic pathway is not involved.

Where the CB2 receptors are located is one of the main differences between the CB1 and CB2 receptors. The CB2 receptor is located in the immune system and the cells derived from the immune system. They are found in the highest concentration on the spleen (also found in the tonsils and thymus gland), and they function primarily for anti- inflammatory responses. The CB2 receptors are most likely active in immune supression. While this may seem counter productive, there are many autoimmune disease where the body’s natural immunity begins to attack healthy cells. The anti-inflammitory component of the cannabis have been influential in developing treatments for demylenating disorders such as multiple sclerosis and Parkinsons’s disease.

There is large amounts of evidence that prove researchers have discovered the mechanisms of action of the cannabinoid receptors. The CB1 receptor is activated when THC binds to the active site of the receptor. This inhibits the enzyme adenylate cyclase, which is responsible for converting ATP to cAMP. Cyclic AMP (cAMP) is the secondary messenger for protein kinase A therefore passively shutting down the A-type potassium channel (rapidly activating voltage-gated channels). The A-type potassium channel is responisible for numerous functions; some of them include regulating neurotransmitter release, epithelial electrolyte transport, smooth muscle contraction, insulin secretion, heart rate, neuronal excitability, and cell volume. Another type of potassium channel that the CB1 receptor effects is the inwardly rectifying potassium channel. This is a potassium selective ion channel that is responsible for regulation neuronal activity and establishing the resting membrane potential of the cell membrane. Because this potassium channel is activated by a G-coupled protein receptor it suggests that the channel is activated by the beta and gamma subunits of the heterotrimeric G protein complex.

Another way that THC replicates the anandamide receptor system in the central nervous system is that it directly inhibits N and P/Q-type voltage dependant calcium channels and sodium channels. These channels are responsible for the release of neurotransmitters at the presynaptic cleft. Inhibiting these channels would prevent the influx of sodium and calcium and therefore inhibiting the release of neurotransmitters, L- glutamate, GABA, noradrenaline, 5-HT and acetylcholine. These neurotransmitters are normally released into the synapse and either taken back up by the synapse or by the adjacent cell, but many drugs either prevent the reuptake of neurotranmitter (therefore leaving more to be taken up by the other cell) or they modify the presynaptic terminal to release more neurotransmitter than the body would do naturally.

Lastly, one of the major mechanisms of action of THC in the brain is to activate the mitogen-activated protein (MAP) kinase enzyme. This pathway is known to contribute to regular cellular activites, inculding; gene expression, cell proliferation, differentiation, and ultimately the apoptotic pathway. This pathway could be intrumental in discovering the anti-tumor properties of the cannabinoids. Scientists have found that the cannabinoids, when binding to mutated/cancerous cells that they signal the cell to “commit suicide” because it has not copied its faithfully. This would ultimtely decrease the instance of cancerous cells among patients. THC has provent to regulate the release of neurotransmitters in the brain; there is evidence that THC is a neuroprotective agent.

New Medicinal Marijuana Findings

The impact of a new study are leading researchers at the National Institutes of Mental Health in Bethesda, Maryland to discover that cannabinoidol and THC are cannabinoid receptor independent, which means that cannabinoid receptor agonists do not affect their ability to bind. They also discovered that “cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry.” This is is important in glutamate excitotoxicity because it has been show that antioxidants can prevent glutamate from reaching toxic levels. A Dutch team of scientists from Utrecht University studying how to prevent neurodegeneration by using THC found results that were similar to previous findings. They also found that “cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures.” This finding would be particularly helpful for patients suffering from cerebral ischemia because there is always a risk of creating highly reactive oxygen chemical molecules when an oxygen depreived region of the brain with oxygen.
 
CB1 receptors are predominantly found in the brain in the basal ganglia and the hippocampus. They are also found in the cerebellum, and the male and female reproductive organs.

So does that mean when I get high, so does Mr. Happy? Yes, leave it to little dirty Johnny to read an entire scholarly article and pick out the one reference, no matter how oblique, to genitals! HAHAHA :science::nut::smilie-devil:
 
What does marijuana do? It rebalances everything

The “simplest” accurate description of the effects of marijuana in humans is that it modulates the regulation of homeostasis. Homeostasis is what Goldilocks seeks in the children’s story: not too hot; not too cold; just right. More than just heat and cold, the human body contains many systems which must be held in relative balance. The balance between inhibition and excitation, bone formation and resorption, inflammatory/anti-inflammatory signalling, fat storage and release, blood sugar, blood pressure, hormone levels; all these systems are held in balance by the endocannabinoid system. This system, though involved in maintaining nearly every biological process in all humans, has only received scientific study for roughly the past 20 years, and it was discovered because it’s the site of action for marijuana.

Marijuana does not simply activate (agonise) this system. In addition to full cannabinoid agonists (chemicals which stimulate — agonise; antonym: antagonise — receptors), it also contains partial agonists, antagonists (Thomas, 2007), reuptake and transport inhibitors, enzyme modulators and much else besides, (Russo, 2011) including an assortment of terpenoids and flavinoids responsible for the odour of the flowers; how a marijuana strain smells indicates what mix of chemicals (all of which appear to be pharmacologically active in humans) are present, beyond the most famous two, neither of which have an odour: THC and CBD. The most studied receptors in the endocannabinoid system are called CB1 and CB2, both of which inhibit the other (Callén et al 2012), and both of which are stimulated by THC (a partial agonist at both and other sites) and antagonised by CBD (Thomas et al, 2007). There are also believed to be numerous other receptors involved (Petrocellis, 2009), and their scientific study is yet only preliminary and largely speculative. Far from a single chemical with a single mode of action, marijuana has an entourage effect: many chemicals working together to produce effects not reducible to the action of only one or two of its constituents. One chemical it often contains in relatively large quantities, for example, is caryophyllene, a selective full CB2 agonist which is also found in cloves, rosemary, hops and eucalyptus. Other plants which work on cannabinoid receptors include hot pepper and vanilla. Through their presence in the diet of some marijuana users, these (and other) plants participate in the entourage effects of marijuana in modulating the regulation of homeostasis.

Summary: it rebalances almost every system in the body through multiple inter-related effects which move in several directions at once and which compensate for each other’s effects (confused yet?)



But what does it all DO?

Research into the effects of marijuana has been aided by intense and widespread public interest, but hindered in recent decades by efforts by various parties to suppress any investigation into possible benefits and to spread claims of possible harms (no matter how tenuous), as part of the “war on drugs.” As an ethnographer working with young drug users in person and on the internet, as well as having read widely on the subject, these are the effects I have most often found credibly attributed to marijuana:

Increased appetite, change in the perception of time, relief from pain, intensified awareness (both inside and outside the body), relaxation, euphoria, increased heart rate, lower blood pressure, emotional release, increased vigor, lethargy, inhibited memory, increased creativity, intense introspection, reveries, flights of fancy, lower body temperature, increased sexual pleasure, reduced sexual desire, relief from nausea, greater aesthetic appreciation, magical thinking, heightened interest in spiritual phenomena, and both increased and decreased anxiety (presumably different types of anxiety).

Reported medically relevant effects of marijuana also include bronchodilation, decreased intracranial and intraocular pressure, glucagon release, reduction in insulin tolerance, lymphocyte suppression, antimicrobial, anticonvulsant, antipsychotic, psychotomimetic, anti-inflammatory, antiemetic, antinociceptive and anticarcinogenic effects.

Occasionally marijuana causes many strange and idiosyncratic effects not here described. Some of these may sometimes be labelled as psychotic or spiritual, but these effects are typically short-lived; they do not last and often cannot be produced reliably or consistently, making them difficult, if fascinating, to study.

Many of marijuana’s effects appear to be highly context- and dose-dependent. In small and occasional doses, it is often more stimulating, boosting appetite and providing relief from depression, whereas in very large and frequently repeated doses, these effects may reverse, with less appetite and relative inactivity. While it influences every organ system, its direct effects are largely confined to the maintenance of homeostasis, which it pushes not just in one direction but in several, counteracting and balancing out its own effects. Even a massive overdose will generally have a negligible impact on long term health, though it may be disorienting until it wears off.

The stimulating effects of THC typically last 2-3 hours, whereas the half-life of CBD, which is more relaxing, is 9 hours. Thus, the first dose of marijuana after a period of abstinence will tend to be far more stimulating than subsequent doses, which must compete with the relaxing effects of previous doses, because the relaxation both persists much longer and shares many of the same pathways as the stimulation. Regular ingestion of THC also leads to increased tolerance to its stimulating effects, but not to its relaxing effects, with very heavy use associated with a reversible 20% reduction in CB1 receptor density in some areas of the brain (Hirvonen et al, 2012); THC itself provides a longer term mild relaxing effect than the immediate boost. As cannabinoid activity can produce anxiety, it may well be that developing tolerance to the drug may itself protect against anxiety on a longer time scale; in a sense, by getting high you can get your anxiety out of the way while also benefiting from a variety of relaxing and euphoric effects to counteract it, rather than having to deal with constant, unremitting anxiety. Notably, Hirvonen et al only found the reduction in receptor density in only some areas, so this long term down-tuning does not affect all of the processes influenced by THC, but only some of them. In any case, we need to consider not just the immediate high, but also its persisting effects, if we are to understand the consequences of its use in humans.

Summary: it does lots of things, and sometimes also the opposite. (maybe this will be easier if we go system by system…)




Marijuana in the Brain

The brain’s major inhibitory neurotransmitter is GABA, and the major excitatory neurotransmitter is glutamate; the endocannabinoid system regulates the levels of each of these by selectively suppressing them as called for, hopefully maintaining an appropriate balance. THC temporarily boosts this process, suppressing both inhibition and excitation. With GABA suppressed, a wide variety of effects and processes which would otherwise have been inhibited become more free to play themselves out. This explains the sensory enhancements commonly experienced by marijuana users, with increased sensitivity to smell, sight, sound, texture and much besides, including sexual pleasure. This is probably also the best scientific explanation for its occasionally outlandish effects, from the merely weird to the deeply spiritual to the profoundly unsettling: the mind, unleashed and uncontained, for better or for worse. Glutamate, though itself excitatory, excites neural networks which inhibit various behaviours, and so its suppression may contribute not only to relaxation but also to some of marijuana’s behavioural effects, such as indulgence in magical thinking and the wild dancing. Importantly, glutamate can also damage brain cells (excitotoxicity), and so suppressing it provides some protection brain damage as it occurs in head injury, epilepsy, hypoglycaemia, stroke, alcohol or benzodiazapine withdrawal and a variety of neurodegenerative conditions including multiple sclerosis, Parkinson’s Disease, Alzheimer’s Disease and Huntington’s Disease, among other conditions. Cannabinoid receptors on glial cells are involved in memory storage, recall, and forgetting (Lane et al, 2005), as well as the extinction of conditioned place preferences more specifically (Parker et al, 2004), suggesting that marijuana use may make it easier to adapt to new contexts and to forget old habits. It fundamentally changes how we experience the passage of time; in Hindu mythology, Lord Shiva, poisoned by time, takes marijuana which relieves his anxiety so that he begins to dance, and through his dance the poison is neutralised, thus saving the universe from being destroyed by an imbalance between space and time. Many experiments have shown that marijuana use impairs performance at certain memory tasks, but that this effect disappears after a period of abstinence, and so cannot be described as damage. Rather than merely the absence of remembering, forgetting is an active process by which we let go of extraneous or harmful memories (White, 2001; Pollan, 2002); by boosting forgetting functions through its effects on glial cells, marijuana may provide relief from traumatic memories. (Marcisano, 2001) The creative benefit most commonly cited by artists who use marijuana is in improvisation, getting into the flow so that strange new rhythms can emerge, fascinate and delight. (Fachner, 2003) More research is necessary, but I suspect that increased forgetting and increased improvisation are linked, and that a good description of marijuana’s creative effects might be less rote repetition and more novel recombination; whether that will be desirable or harmful will depend on the task at hand.

Marijuana is very popular among people with ADHD, for whom it may be synergistic with their tendency to hyperfocus, sometimes used to push past ennui into full dynamic engagement (the term for which in the cognitive sciences is “flow”), though it also tends to increase restlessness and can make them even more distractable, especially in larger doses, and so ADHD people often find very small doses to be the most helpful. (Loflin, 2014) One physiological description of ADHD is impaired dopamine transporter function, and the most common pharmaceutical interventions for ADHD are psychostimulants such as amphetamines which stimulate dopamine release directly. Marijuana, on the other hand, does not increase dopamine signalling, but modulates salience through other pathways. For this reason, many ADHD people find that marijuana feels more “natural,” ebbing and flowing with the context, whereas amphetamines often feel forced or artificial. Another difference is that amphetamines often make it very difficult to eat and sleep, whereas marijuana boosts appetite and, for many of its users, provides unusually restful and easy sleep. This is extremely important, because poor sleep and poor diet are major sources of harm among people with ADHD.

Some autistic people have also found marijuana to be of benefit in relieving the overstimulation-related emotional anxiety and tension which can inhibit their behaviour. Recent evidence has emerged that autism may in part be caused by abnormalities in cannabinoid signalling (Földy, 2013), so it seems that the rebalancing effect of marijuana directly interacts with some of the underlying causes of autism. One physiological description of autism is too much glutamate and not enough GABA; by suppressing both glutamate and GABA, marijuana may essentially level the playing field, so that a stoned neurotypical and a stoned autistic person end up on roughly the same level.

In neither ADHD nor autism does marijuana merely suppress symptoms and make a person “normal”; far from it. What it does is to rebalance many metabolic, attentional and neural systems, reconfiguring any problematic balance which may be in place, and producing a new state of consciousness unlike either neurotypical consciousness or the typical expression of either ADHD or autism. That is, it may normalise homeostasis, but to do so is not necessarily normative, in the anthropological sense.

In summary, marijuana rebalances excitation and inhibition in ways which are sometimes highly valued, and which may correct for or prevent imbalances in attentional and cognitive systems.



Marijuana, Neuroprotection and Brain Damage

In addition to preventing glutamate excitotoxicity and neuroinflammation, marijuana also reduces the volume of fluid in the head following head injury, lowers brain temperature (trivia: the popular fever reducer sold as Tylenol works partially by breaking down into a cannabinoid reuptake inhibitor, and therefore shares a pathway with marijuana (Bertolini, 2006)) and prevents prion accumulation (Dirikoc et al, 2007), all of which are ways by which it’s known marijuana can protect against brain damage. It also reduces risk of such neurodegenerative conditions as Parkinson’s Disease and Alzheimer’s Disease through other mechanisms besides. (Ramirez et al, 2005; Eubanks et al, 2006) However, because of the pressure from the US government to publish (or fabricate) harms from marijuana, several widely publicised studies have been used to claim that marijuana causes brain damage. In every case, these studies either suggested nothing of the kind when properly interpreted, or were confounded enough to be worthless, and there is, at time of writing, absolutely no credible evidence of any form of brain damage from marijuana use in humans. In a classic example, one team of researchers forced rhesus monkeys to inhale large volumes of smoke, depriving them of oxygen in the process, and attributed their mental decline to marijuana rather than to oxygen deprivation. (Heath et al, 1980) Not surprisingly, subsequent studies failed to reproduce their finding. (Slikker et al, 1990; Paule et al 1992) Other studies have shown mental deficits and brain abnormalities in some young heavy marijuana smokers (Meier, 2012; Smith, 2013, Gilman et al 2014), but it’s highly likely that both the observed deficits and the marijuana use were caused by the same factor, rather than the deficits being caused by the marijuana use, as the deficits are only found in a minority of teenagers who use marijuana, and because there are a variety of sources of deficit which also predict marijuana use. (Tims, 2002) Post traumatic stress disorder (PTSD; often a product of child abuse) is a likely candidate, because it predicts both cognitive deficits (Moradi et al, 2013) as well as adolescent drug use (Maté, 2008; Dube, 2003), including heavy cannabis use. (Cornelius et al, 2009) For people with PTSD, marijuana may correct a chronically dysfunctional stress response (Heim et al, 2000) and make it easier to forget painful memories (Ganon-Elazer 2012; Patel et al, 2004; Marcisano et al, 2001). Regrettably, in none of the studies in which deficits were shown to be correlated with heavy early-onset marijuana use did researchers attempt to control for the enormous confound of past trauma. In light of the indications that marijuana is useful in the treatment of PTSD, to attribute the harms of trauma to a plant being used to alleviate it is particularly bothersome. There has also been a disturbing tendency in news coverage report all findings of alteration as “damage,” even where no deficits, and indeed some potential benefits, were shown. Given the ongoing drug war and propaganda efforts by various governments, the utmost skepticism is warranted in interpreting claims of marijuana-induced brain damage, none of which (to date) survive careful scrutiny grounded in the appropriate scientific literature. Given what we’ve learned about marijuana’s effects the dire claims seem ever more preposterous, especially given the many marijuana users who have distinguished themselves in scientific and artistic communities alike.

Rather than simply accusing hemp flowers of harming teenagers, a more sensible approach might be to listen to teenagers who are heavy marijuana users, to understand why they’re using it and what they’re getting out of it, bearing in mind that they may well be survivors of abuse, which agents of the legal, medical and educational systems may have directly participated in rather than alleviating. Stigma, theft of medicine, segregation and punishment are unacceptable responses to observed suffering.

In summary: marijuana rebalances and soothes a variety of neural processes and can protect against numerous potential sources of damage. No form of brain damage has been demonstrated to have resulted from its use.



Marijuana and Metabolism

The endocrine system consists of glands throughout the body which regulate everything from energy levels to metabolism to sex drive. CB1 receptors can be found throughout this system and influence the release of many hormones. One function of this system is to produce excitation in response to stress. This is necessary for survival, but when it gets out of hand it can be a major source of harm, especially in a fast paced modern economy where stress may be relentless. One effect of marijuana in the endocrine system seems to be to protect against this, by reducing susceptibility to stress-induced activation in the hypothalamus-pituitary-adrenal axis. (Patel et al, 2004) The details of how it does this, as well as all of its other diverse and complex effects throughout the endocrine system, however, remain murky, but are becoming clearer and will likely continue to do so over the coming years.

Marijuana’s ability to boost appetite is well known, and it is used to treat anorexia as well as diet problems resulting from other drug therapies, such as in patients with AIDS or cancer. Part of this effect on appetite may be because GABA suppression increases the rewarding stimulation from food; another part is its ability to block nausea, including the nausea induced by chemotherapy drugs. While there is a stereotype of getting high and then gorging on lots of delicious food, many of my respondents have informed me that they actually prefer to get high after their meal, finding it to improve their digestion and settle their stomach. It’s also common for “the munchies” to not set in until around 45 minutes after dosing, and it’s here that the endocrine effects, specifically in the pancreas, are explanatory. The pancreas secretes the pair of hormones glucagon and insulin to regulate blood sugar by signalling the liver to break down fat into sugar (glucagon) or to store sugar as fat (insulin). These hormones work as a pair to maintain homeostasis, and they stimulate the release of each other through a complex feedback mechanism. In 2008, it was determined that CB1 activation triggers glucagon release and that CB2 activation lowers glucose-dependent insulin release. (Bermudez-Silva et al, 2008) This helps to explain why marijuana users tend to eat more calories but do not gain any extra weight, have less obesity and lower rates of type II diabetes than non-users (Rodondi et al, 2006; Le Strat, 2011; Rajavashisth et al, 2012), and why some diabetics find that marijuana makes it easier to manage their blood sugar, as marijuana rebalances the relative levels of glucagon and insulin, although anti-inflammatory effects are also relevant. Type II diabetics (whose pancreas still functions) tend to have very high levels of insulin, but the liver is unable to use it, and so blood sugar stays high, and the pancreas damages itself by trying to continually produce more and more insulin, eventually leading to organ failure if the diabetes is unmanaged. By boosting glucagon release and lowering insulin resistance, marijuana may alleviate or prevent the progression of type II diabetes and restore balance to the system. The endocannabinoid system is also separately involved in fat storage (Cota, 2003; Osei-Hyiaman et al, 2005) (interestingly, THC is also fat soluble, and so it seems to be storing itself through this process, and is released back into the bloodstream during exercise (Wong et al, 2013)), and some studies have found marijuana users to have more fat in visceral tissue. (Hézode et al, 2008; Muniyappa, 2013) Cannabinoid antagonists have also been shown to reduce obesity, and not only do rodents given these drugs eat less, they also lose more weight than their reduced feeding can account for. (Pagotto et al, 2006) What exactly this means for users of marijuana (which contains both cannabinoid agonists and antagonists) remains unclear (more fat storage through one mechanism, and less fat storage through another), but the findings of lower rates of obesity and diabetes among marijuana users — despite correlations between marijuana use and a variety of life-style risk factors, including heavier eating — are very promising. Marijuana use is certainly not a major source of harm in this system, and may be of benefit in a variety of (very common) circumstances.

Cannabinoid signalling is also involved in many reproductive functions in both males and females, including in foetal development, and there are even CB receptors on sperm themselves. While the effects of marijuana on sperm and reproductive functions are not well understood, it appears that regular marijuana use may moderately reduce both menses and sperm production, and that therefore while many marijuana users can still conceive, it may be prudent for couples having difficulty conceiving to refrain from using marijuana. On the other hand, many find marijuana to improve their experience of sex, and it even allows for orgasm in some otherwise anorgasmic women. Not enough is known about its effects on pregnancy to be confident as to when it may be of benefit or harm to the foetus, (Pagotto et al, 2006) but it is commonly used to alleviate the nausea associated with morning sickness.

A stereotype of marijuana users is that they are lazy and that the drug makes them inactive. Traditional Hindu practices assume that this is the case, and discourage its use by home-owners, while allowing it to ascetics in the process of renouncing worldly attachments. (Morningstar, 1985) Some marijuana users certainly seem drawn to renunciation, and may show little interest in material advancement, especially when using heavily. Many others, however report that its effects are stimulating, and there have been many elite athletes who used marijuana, including martial arts legend Bruce Lee, basketball legend Kareem Abdul-Jabbar, Olympic gold medallists Michael Phelps and Ross Rebagliati, and more than half of the Oregon Ducks football team. Clearly, its effects are not disastrous to fitness or to the ability to exercise. Noted astronomer Carl Sagan and physicist Richard Feynman both used marijuana to stimulate visionary states and the flow of ideas; a great many other musicians, writers, scientists and artists have admitted to doing so as well. Many of the same have admitted at other times that marijuana can interfere with their performance or leave them distracted and tired. Its effects can be very inconsistent, and depend on the user’s metabolism, dosing strategy and the chemical composition of the strain being used.

In summary, marijuana rebalances energy levels, fat storage, reproductive functions, appetite and metabolism, and can correct for imbalances such as in type II diabetes, anorexia and a variety of stress-related disorders.



Marijuana and Mental Health

The use of marijuana is often seen in people who suffer from a wide variety of mental health problems (Wittchen et al 2007), for which it is often used to self-medicate, for better or for worse. It is known to sometimes relieve depression (Denson, 2006), emotional anxiety (Fusar-Poli et al, 2010) and intense stress (Ganon-Elazer, 2012). However, through its powerful and pervasive effects, it may well trigger an episode of any number of conditions, such as underlying psychoses. Some use marijuana precisely to provoke an inexplicable or extreme mental state, which may be interpreted as either spiritual or psychotic, or to produce greater and longer lasting states of elation and activity (mania), and many religious and shamanic groups have employed it to facilitate communication with spirits, to transport the user to heaven, to destroy karma, to deepen a trance, and much else besides. Marijuana surely is a drug favoured by lunatics and maniacs, not only to end their lunacy or mania but sometimes to provoke it. Does that make it dangerous to people who do not want these effects? Especially, perhaps if they despise the moon?

Much has been made of the association between cannabis use and schizophrenia. Schizophrenia (literally: broken mind) is a diagnostic category which consists of an unknown number of poorly understood mental types, characterised by positive symptoms such as delusions, hallucinations and disordered thinking, and negative symptoms such as not finding pleasure in anything and not being interested in talking to the other humans. Best estimates suggest that around 1 in 100 people will be exhibit schizophrenia at some point during their life, or 1.4 in 100 people who have ever used marijuana. (Zammit, 2007) This makes it a moderate risk factor, but less severe than being a first or second generation immigrant, having a father over the age of 55 at the time of birth, being raised in an urban area, or infection with Toxoplasma gondii, a parasite common among cat owners. (Bourque et al, 2011; Torrey et al, 2012) All of the above effects are dwarfed by familial predisposition, and Proal et al recently found that schizophrenic marijuana users are just as likely to have schizophrenic relatives as schizophrenics who do not use marijuana, suggesting that marijuana is not a cause of schizophrenia at all, but it’s just that schizophrenics are more likely than non-schizophrenics to use marijuana. (Proal et al, 2014) If we wish to reduce risk factors for schizophrenia, we may be better served by banning cats. Other research has suggested that “cannabis induced psychosis,” most characterised by paranoia, is at least partially a direct result of legitimate paranoia occasioned by the war on drugs, rather than the plant itself. (Hamilton et al 2014) There is some evidence that marijuana users with psychosis display more positive symptoms (such as paranoia) and less negative symptoms (such as anhedonia) (Zammit, 2008); this is especially interesting because mainstream psychiatry lacks an effective treatment for the negative symptoms, and it may be that many people are self medicating with marijuana for precisely this reason. Not only do people with psychosis use more marijuana than people without psychosis, but Giuffrida et al found that the body may be responding to schizophrenia by increasing endocannabinoid expression, and that this was associated with a reduction in symptom severity. (Giuffrida et al, 2004) Should we be surprised that some schizophrenics are drawn to a plant which mimics some of the body’s defence mechanisms against their symptoms? Lastly, while THC may occasionally produce psychotomimetic effects (that is, very stoned people may appear to be psychotic until they sober up), CBD appears to be anti-psychotic, (Zuardi et al, 2006) and so modulating the endocannabinoid system, for example with a high-CBD strain of marijuana, may be clinically useful in managing the positive symptoms of psychosis as well as the negative ones. In short, the evidence does not support the claim that using marijuana puts you at greater risk for harms from psychosis; perhaps even the opposite is the case, but more research is necessary. Indeed, prohibition is, itself, undeniably a far greater source of harm, for example by severely exacerbating such problems as racial oppression. (Fellner, 2000) Whether the same would be true for the prohibition of cats remains to be tested.

Among people living under the description of bipolar disorder, marijuana is the number one drug of choice, and those who use marijuana have less depression and more mania than those who do not. (Leweke, 2008) This is not surprising, given marijuana’s potential to increase positive symptoms and decrease negative ones. As there are strong cultural forces which value the creativity and charisma of mania and demonise depression, and because people living under the description of bipolar disorder typically identify with their hypomanic self rather than with a sober baseline, (Martin, 2007) marijuana is often used to improve mood and productivity, as well as to deal with stress in highly demanding contexts, with occasionally destabilising or dangerous consequences. To understand its effects in bipolar disorder, therefore, it is necessary to compare its users to others facing similar contexual pressures — for example, are university students (or entrepreneurs) more or less likely to “burn out” if they use marijuana? It’s also important to remember that marijuana has anti-depressant effects and is used to produce stimulation among people who do not have bipolar disorder, as well as by those who do. It’s not surprising that people with bipolar tendencies use it for the same reasons that others use it, even knowing it may increase the likelihood or intensity of a manic episode. Such people would do well to monitor their use (or to recruit friends and family to help monitor their use), and to consider refraining from using if they have a history of making dangerous decisions while manic.

In summary, marijuana rebalances mood, anxiety and attention in ways which may correct for or prevent certain forms of imbalance, but which may also upset a tenuous balance.



Marijuana in the Heart and Lungs

Much attention has been paid to the effects on the lungs of smoking marijuana, because of the severe and well known harms from smoking tobacco. Marijuana smoke contains many of the same carcinogens as tobacco smoke, and some in far higher concentrations (Moir et al, 2008), and so it was expected that it would be a cause of lung disease, as those chemicals are believed to cause cancer and emphysema in tobacco smokers. This however turns out not to be the case; marijuana smokers do not have elevated rates of lung cancer or emphysema, the two main debilitating effects of chronic tobacco smoking, and none of its long term effects on lung function are of clear clinical significance. (Tashkin, 2013) The analogy therefore can be rejected: marijuana is not dangerous in the ways that tobacco is dangerous. In fact, tobacco smokers who also smoke marijuana have lower rates of cancer and emphysema than do tobacco smokers who do not smoke marijuana, (Aldington, 2007) suggestive of the medicinal and/or protective effects of the flower vapours. Some marijuana smokers experience significant irritation and pain in the lungs which worsens over years of smoking, which may lead to a severe cough, and which is consistent with chronic bronchitis, but this often disappears if they switch from smoking to vaporising, even after decades of heavy smoking (vaporising is a method in which the plant matter is heated enough to convert the active compounds into a gaseous form, but below a temperature which would burn the plant matter, thereby avoiding the toxic byproducts of combustion). The lack of association between marijuana smoking and cancer, despite the well documented ample presence of known carcinogens, is strong evidence of its anti-carcinogenic effects; the chemicals it contains seem to compensate for the harmful effects of smoke inhalation (this is far from the only evidence of anti-carcinogenic effects (Ligresti et al, 2006), but it is suggestive as to their extent and efficacy in the wild). Marijuana, as a bronchodilator and an anti-inflammatory, has also been used in the treatment of asthma, and many asthmatic marijuana users have reported that their symptoms reduced during their period of use. (Williams, 1976)

Another major cause of death in tobacco smokers is heart disease, and, like the lung effects, there’s no evidence of elevated levels of coronary disease in marijuana smokers, despite the presence of various toxins in marijuana smoke. In the heart, the effects of marijuana are quite clear: decreased blood pressure, increased heart rate, often by as much as 30% , with CB1 and CB2 receptors as elsewhere working in opposite directions to control blood vessel dilation and other aspects of cardiovascular function. For most users this is not an appreciable concern, although it’s not uncommon for marijuana users to abort exercise because of strange feelings in their heart, or specifically because they feel that their heart is pumping too quickly or strongly. Some people with chronically low blood pressure find that they react badly to marijuana, and it is common for people under the acute influence of alcohol — which also lowers blood pressure — to become dizzy or nauseous if they proceed to smoke marijuana. Doing so may result in “the spins,” a very uncomfortable feeling where the world appears to be spinning and only spins faster if one closes one’s eyes. It is highly advisable therefore not to smoke marijuana while already drinking, especially if one is not a regular marijuana user and may be taken by surprise by the blood pressure crash. Smoking and then drinking does not appear to be nearly so dangerous, partly due to relative ease of dose control (you can sip your drink, but you cannot unsmoke a joint).

In people at elevated risk, a heart rate boost of 30% can trigger a heart attack. It has been estimated that marijuana smoking may increase risk for the next hour of myocardial infarction (heart attack) by a similar extent to having sex or exercising. Therefore, if your doctor has told you to abstain from sex due to the danger to your heart, you should consider also abstaining from marijuana. However, just because it’s more likely for a heart attack to take place during that window doesn’t mean it increases the risk of a heart attack happening at all. Indeed, a study of 3886 people who had already had at least one heart attack found no statistically significant association between marijuana use and death over an 18 year period (Frost et al, 2012), so there’s no great cause for worry. Instead, it seems to be the case that, if someone was going to have a heart attack anyway, it’s liable to happen within an hour of getting high, because of marijuana’s circulatory effects. CB1 activation has also been shown to worsen the damage from repurfusion (the shock caused by oxygen returning to cells temporarily deprived of it due to a heart attack), whereas CB2 protects against this damage, as well as against plaque instability and inflammation, such as in atherosclerosis (remember, THC activates both CB1 and CB2, so it both helps and hinders at the same time). CBD, meanwhile, has other non-cannabinoid receptor mediated cardioprotective effects. A high-CBD strain of marijuana may therefore be more beneficial for people at risk for heart attack than a high-THC strain. (Russo, 2006) For those concerned about heart and lung effects, vapourising or eating marijuana may be preferable to smoking it, as that will greatly reduce exposure to a variety of toxins. That said, the appropriate level of concern for smoking marijuana is probably more comparable to the dangers of toasting bread instead of eating it raw than it is to smoking tobacco, and many users will continue to consider this an acceptable trade-off for the convenience and ease of dose-control which come from smoking. (Montecucco, 2012)

In summary, marijuana rebalances dilation and contractility in the heart and lungs and may correct for or prevent such imbalances as usually result from smoke inhalation.



Marijuana in the Bones, Muscles and Joints

Unlike the many hard objects we encounter outside the body, our bones are constantly being broken down and remade. In young people there is typically more growth than break-down; this levels off and then reverses with age, and, as bone formation is driven by estrogen, post-menopausal women, women who have had their ovaries removed, or others who have very low estrogen, are at increased risk of bone loss and fracture. Cannabinoids regulate this system, stimulating bone formation via CB1 activation and slowing the rate of break-down via CB2 activation, and so marijuana may compensate for factors which could otherwise drive osteoporosis. (Scutt, 2007; Bab, 2009) As an anti-inflammatory and muscle relaxant, marijuana can also improve flexibility and provide relief for everything from soreness after exercise to certain types of arthritis. Indeed, endocannabinoid activation has been found to occur naturally following exertion, and is believed to allow for longer periods of exertion in what’s known as the “runner’s high.” (Sparling et al, 2003) I have observed marijuana use in the wild stimulating the user to begin exercising or facilitating continuation of exercise despite fatigue. I have also seen the opposite: half hearted attempts at exercise followed immediately by cessation. On the one hand, it may be that marijuana makes it easier to continue doing what one was already doing, such as either running or lying on the couch. On the other hand, it sometimes triggers a reversal, from low energy to high energy or vice versa. Like the endogenous runner’s high, using marijuana when fatigued may produce a “second wind” and allow the user to continue. The cardio-pulmonary dilation, discussed above, is also relevant, as it may improve oxygen availability during exercise.

In summary, marijuana rebalances bone growth, muscle fatigue and inflammation in ways which may correct for or prevent certain forms of imbalance, such as age related bone loss and pain after exercise




Marijuana and the Immune System

THC has been experimentally shown to inhibit certain immune functions — in particular, lymphocyte activity — and to augment others, (Cabral, 2001) and marijuana also contains a variety of antimicrobial agents. (Nissen, et al, 2010) These immunological effects can protect against numerous auto-immune disorders, increase healing and down-tune immune responses. It is likely the case that marijuana can protect against certain kinds of infections under certain conditions, and that it can increase vulnerability to other infections under other conditions. Cannabis oil, especially applied topically, may be an effective treatment for acne, psoriasis (Wilkinson 2007), contact dermatitis (Karsak et al, 2007) as well as a variety of other inflammatory or allergic responses, and against certain infections because of its direct anti-microbial effects.

In summary, marijuana rebalances inflammation and other immune responses and may correct for or prevent certain forms of imbalance, such as autoimmune disorders.

Conclusion:

Marijuana has very complicated effects throughout the body. Many of these effects are often highly valued and sought for a wide variety of reasons. Some of these effects can in some situations can be undesirable, and THC by itself has been implicated in a variety of potential harms, including anxiety, psychosis-like mental effects, heart attack and immune suppression. It is necessary therefore to emphasise the importance of using cannabis flowers instead of isolated chemicals such as pure THC, because of the ways in which the other chemicals in the flowers compensate for, counteract, or amplify the effects of THC. (Russo, 2011) Whether marijuana will boost or inhibit each bodily system depends on the state of the body at the time of use, the chemical makeup of the marijuana being used, and the dosing strategy. Smoking one small hit one evening per week may well have the opposite effect of consuming cannabis oil throughout the day every day; the former may be primarily stimulating whereas the latter may lead to a generalised relaxation and slowing of metabolism. As either/both may be desired by each user, preferences in plant variety and dosage strategy vary accordingly. Some people react badly to the plant, whether for mental, cognitive, hormonal or ideological reasons, and some are allergic to it; for many others, it can be profoundly helpful, providing a way by which to take some conscious control over the regulation of homeostasis and to seek a balance which will work for us.


The above is my best understanding of what marijuana does. Although I have here leaned mostly upon scientific journal articles, which I have tried both to understand and to interpret, I am not in fact an advanced specialist in every relevant discipline — nor, I suspect, is anyone else; my academic background is as an ethnographer, and so I consider my primary responsibility to be towards the humans using the plant, for whatever reasons, and with whatever consequences, and I engage with the scientific literature in order to better understand and interpret the observations I have made in the wild, the many curious things I have been told in interviews both formal and informal. I am absolutely certain that there is very important information about the effects of this plant which I do not understand or which I have not yet seen. If you know of anything useful, or suspect that something I have said is inaccurate, incomplete or in other ways merits revision, I would be happy to hear your suggestions. May my best endeavours to faithfully convey my observations be useful to you.

Happy 420!
Can you smell the flowers?

Funding:
None. Some years ago I took a vow never to sell any drugs about which I expected to write, so as to avoid conflict of interest. I am, however, almost completely out of money, and would be very appreciative of donations and/or job offers so that I can continue to live, buy groceries, learn and write. (no paypal; can accept email money transfers to michaelvipperman@gmail.com, or food offerings in Toronto area only)

Donations received as of 8:45 PM, May 2, 2014: $10.

Acknowledgements:
Proof reading provided by James Birch, Lav Dimitrije and A.C. Patterson.

I own the rights to none of the images.

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Cannabis And The Brain Part I: It’s About THC (Sort Of…)
By Joshua Kaplan | Sep 8, 2017

If only studying marijuana's effects on the brain were as easy as researching alcohol.

Throw back a shot of whiskey or tequila or vodka, and you’ll feel a bit buzzed. After 5 shots, you’ll be drunk. With spirits, it’s all about the ethanol content. The more ethanol you consume, the drunker you become. It doesn’t matter if you have 5 shots of 80 proof vodka or of 80 proof whiskey, ethanol is going to have the same effect on brain function regardless of the distillation process.

This makes studying alcohol in the lab straightforward. When mice get drunk on 190 proof ethanol mixed with water, or mixed with sugar water (think Smirnoff Ice), scientists can generalize the effects to those from humans pounding drinks at the company Christmas party.

Marijuana isn’t that simple. Over 100 phytocannabinoids have been discovered in marijuana, and some have actions in the brain. When people talk about “brain actions”, they’re often referring to acting on a receptor, which influences how neurons communicate. It doesn’t imply that these actions make you high. Cannabinoids that make you high are termed “psychoactive” or “psychotomimetic.”

The challenging part of studying cannabis, is that some phytocannabinoids are psychoactive while others are not. Some will counteract psychoactive actions while others enhance them. It can be a mess. So when you take a hit, it’s not just one cannabinoid that affects brain function, but a complex interaction between numerous cannabinoids that produce your state of mind.

THC (more specifically referred to as Δ9-THC) has gotten all the press. Ever since it was first discovered in the ‘60s, THC has been the primary focus of recreational marijuana research. Justifiably so! THC gets you high.

It’s not surprising that cultivation efforts have led to an increase in THC levels over time. A study that analyzed nearly 39,000 cannabis samples found that in THC potency jumped from ~4% on 1994 to 12% by 2014. The 2016 Cannabis Cup even saw four medical grade Indica strains topping the 30% THC potency mark.

Coinciding with the increase in THC potency, there has been a decrease in cannabidiol (CBD) potency. CBD is a phytocannabinoid that can counteract THC’s psychoactive effect, so strains with a high THC:CBD ratio will lead to a more intense high than those with a low THC:CBD ratio. The average THC:CBD ratio increased from 14 in 1994 to around 80 by 2014. The intensity of people’s high can now be higher than ever.

This rapid escalation in the THC potency signals that we’ve entered uncharted territory for understanding marijuana’s short- and long-term impacts on the brain. Conclusions gleaned from early human studies may no longer be valid in today’s high-THC environment. How do you study the long-term consequence of a drug whose composition is constantly changing? It would be like trying to make conclusions about the safety of today’s highways by including data gathered before airbags were invented.

And don’t forget, an increase in THC potency means that other cannabinoid levels will also be altered (as exemplified by the reduction in CBD levels). This shift in cannabinoid concentrations greatly impacts a strain’s effect on the initial high, and its prolonged effect. The high THC potency levels common in today’s weed are thought to be so overpowering that subjective differences must be based on additional distinguishing features. These other features of the subjective experience result from the presence of additional cannabinoids present in the strain and the terpenes they’re dissolved in (terpenes are the fragrant oils that add flavorful qualities to a strain).

And this is where things get a bit complicated.

Marijuana's Multifaceted High
With whiskey, if you evaporate out the ethanol, it no longer gets you drunk. It doesn’t matter if it still retains the oakey, chocolatey notes it once had; the whiskey flavor doesn’t affect how drunk you get. Similarly with marijuana, if you breed out the THC (and consequently its psychoactive metabolites), and crank up the CBD levels, you don’t get stoned.

But with marijuana, the additional cannabinoids can impact how stoned you get, how long it lasts, and the long-term impacts on the brain. While a shot of 80 proof whiskey will you get you equally as intoxicated as a shot of a different brand of 80 proof whiskey, a hit of one strain of weed with a 15% THC potency may have a vastly different effect as a hit of a different strain also with 15% THC potency.

How can two strains with the same THC levels have different effects?

Part II will discuss cannabinoid actions in the brain.
 
Marijuana’s Long Term Effects on the Brain Finally Revealed
October 30, 2017 SatyaRaj

cannabis-brain.jpg



University of Texas just published their research into the long-term effects of marijuana

With a drug war against marijuana still raging in more countries than not, the question of how long-term marijuana use effects the human brain is a pivotal question in its legalization. Although alcohol remains legal despite heaps of evidence to the dangers of long-term use, the fight to make marijuana available both with regard to its medical properties (especially in selectively killing cancer cells) and non-medical uses has frequently hinged on the various claims made about marijuana’s effects on the recreational user.

Luckily, the debate can finally move out from the realm of opinion into scientific evidence as researchers from the University of Texas just published their research into the long-term effects of marijuana use on the brain in PNAS (Proceedings of the National Academy of Sciences).

The researcher helped dispel the dying myth that marijuana use lowers IQ, and actually provides more evidence to marijuana’s potential role in fighting Alzheimer’s. The research revealed that earlier onset of regular marijuana use leads to greater structural and functional connectivity in the brain. The most significant increases in connectivity appear as an individual begins using marijuana, with results showing that the severity of use is directly correlated to greater connectivity.

Although these results will need to be confirmed with a larger sample (this was based on roughly 100 participants), the preliminary results do seem promising. More research will need to be done in order to see if these differences are caused by, or simply associated with, long term marijuana use. They also found reduced gray matter in the OFC (orbitofrontalcortex) in long-term users (which is a brain region associated with addiction). It is unclear whether this region is simply smaller in regular users (explaining their regular use) or if the use actually contributed to structural brain changes. These results will also need to be contrasted with other researcher showing that cannabinoids actually promote brain cell growth

One of the biggest question surrounding marijuana use, particularly by those who try to justify it being labeled a very dangerous and harmful drug, is the potential negative effects of long term use on the brain. Before tackling this question though, it should be pointed out the alcohol remains legal despite a long list of evidence validating that is is clearly dangerous relative to brain wellbeing.

Marijuana, on the other hand, has proven once again to be superior to alcohol, which researchers from the University of Texas demonstrated through research they published in the Proceedings of the National Academy of Sciences (PNAS) regarding the long term effects of marijuana on the brain.
Not only did the researchers debunk the myth that marijuana lowers IQ, and also presented evidence demonstrating that it can effectively fight Alzheimer’s, but they also reveal that regular marijuana use actually leads to greater connectivity in the brain!

Although these study results, which were convened on will have to be corroborated in larger studies, 100 participants, the preliminary results are definitely positive and encouraging.

They also demonstrated another phenomenal finding that it helped reduce gray matter in the orbitofrontal cortex, or OFC, which is the brain region associated with addiction. Another remarkable result!
Although, again, this will have to be demostrated in bigger studies the results are obviously promising. Likewise, cannabinoids were also recently shown to promote brain cell growth (neurogensis) rather than destroy it.

In short, weed makes your brain stronger!

SOURCES:
http://pubs.niaaa.nih.gov/…

http://www.sciencedaily.com/…

http://www.washingtonpost.com/blogs/…

https://en.wikipedia.org/wiki/…

http://www.ncbi.nlm.nih.gov/…
 
Marijuana’s Long Term Effects on the Brain Finally Revealed
October 30, 2017 SatyaRaj

cannabis-brain.jpg



University of Texas just published their research into the long-term effects of marijuana

With a drug war against marijuana still raging in more countries than not, the question of how long-term marijuana use effects the human brain is a pivotal question in its legalization. Although alcohol remains legal despite heaps of evidence to the dangers of long-term use, the fight to make marijuana available both with regard to its medical properties (especially in selectively killing cancer cells) and non-medical uses has frequently hinged on the various claims made about marijuana’s effects on the recreational user.

Luckily, the debate can finally move out from the realm of opinion into scientific evidence as researchers from the University of Texas just published their research into the long-term effects of marijuana use on the brain in PNAS (Proceedings of the National Academy of Sciences).

The researcher helped dispel the dying myth that marijuana use lowers IQ, and actually provides more evidence to marijuana’s potential role in fighting Alzheimer’s. The research revealed that earlier onset of regular marijuana use leads to greater structural and functional connectivity in the brain. The most significant increases in connectivity appear as an individual begins using marijuana, with results showing that the severity of use is directly correlated to greater connectivity.

Although these results will need to be confirmed with a larger sample (this was based on roughly 100 participants), the preliminary results do seem promising. More research will need to be done in order to see if these differences are caused by, or simply associated with, long term marijuana use. They also found reduced gray matter in the OFC (orbitofrontalcortex) in long-term users (which is a brain region associated with addiction). It is unclear whether this region is simply smaller in regular users (explaining their regular use) or if the use actually contributed to structural brain changes. These results will also need to be contrasted with other researcher showing that cannabinoids actually promote brain cell growth

One of the biggest question surrounding marijuana use, particularly by those who try to justify it being labeled a very dangerous and harmful drug, is the potential negative effects of long term use on the brain. Before tackling this question though, it should be pointed out the alcohol remains legal despite a long list of evidence validating that is is clearly dangerous relative to brain wellbeing.

Marijuana, on the other hand, has proven once again to be superior to alcohol, which researchers from the University of Texas demonstrated through research they published in the Proceedings of the National Academy of Sciences (PNAS) regarding the long term effects of marijuana on the brain.
Not only did the researchers debunk the myth that marijuana lowers IQ, and also presented evidence demonstrating that it can effectively fight Alzheimer’s, but they also reveal that regular marijuana use actually leads to greater connectivity in the brain!

Although these study results, which were convened on will have to be corroborated in larger studies, 100 participants, the preliminary results are definitely positive and encouraging.

They also demonstrated another phenomenal finding that it helped reduce gray matter in the orbitofrontal cortex, or OFC, which is the brain region associated with addiction. Another remarkable result!
Although, again, this will have to be demostrated in bigger studies the results are obviously promising. Likewise, cannabinoids were also recently shown to promote brain cell growth (neurogensis) rather than destroy it.

In short, weed makes your brain stronger!

SOURCES:
http://pubs.niaaa.nih.gov/…

http://www.sciencedaily.com/…

http://www.washingtonpost.com/blogs/…

https://en.wikipedia.org/wiki/…

http://www.ncbi.nlm.nih.gov/…
fZBgLQk.jpg

CANNABIS and the MEDICINE in it help's "BIG TIME"!
 
I have a friend at the pool I go to that told me she got uncomfortably high (read panic attack and couldn't come down for hours) from a 10mg gummy.... which I found somewhat hilarious. (I know, I know... I'm going to hell :shakehead:) It takes me 100mg in an edible to actually feel high. Now I realize I'm a habitual user and that my tolerance would be much higher than hers. But that is a significant difference and I have to believe that what the article below infers could be at play here.

How Your Genes Influence Your Response to Cannabis

Ever Smoke the Same Flower with a Friend Only to Have Completely Different Experiences? Your Genes Might Have a lot to do with it
So, you’re at a friend’s house, and they hand you a joint. “Be careful,” your friend warns. “This flower is really strong.” You take a drag and next thing you know, you’re feeling … absolutely nothing.

Sound familiar? It illustrates a pretty common occurrence — the same toke exhibiting different effects in different folks — one for which we might have no one to blame but ourselves. Or, more accurately, our own genes.

Cannabis is able to produce a wide array of experiences in human beings. It can make us sleepy, enhance our relationships, change our perception of the world and relieve the symptoms of debilitating diseases. And while different kinds of cannabis products produce different effects, what is even more interesting is that the same cannabis product can produce very different effects among individuals.

IMG_2141-3-1024x576.jpg


For instance, in passing a joint amongst a group of friends, some people may be completely unaffected while others experience intense intoxication of one variety or another. Why is that?

Cannabis exerts its effects through many targets and mechanisms within the brain, most notably the CB1 and CB2 receptors. These receptors are proteins that are made inside of our cells, and like all other proteins our bodies make, the “blueprints” for how to build them reside in our DNA. Although the human genome (the collection of all human genes) is strikingly similar across people, random or inherited edits (mutations) in these blueprints are extremely common. Genetic mutations can often be the source of inherited diseases, and they can also account for some of the differences in people’s reaction to cannabis.

Mutations in the human CB1 receptor (the target for THC and main site of cannabis intoxication) were first observed more than a decade ago. So far, scientists have identified nine variations of this gene in humans. When the blueprints for the protein are different, the function of the protein is almost always affected.

This means that right now, you’re walking around with one of at least nine different versions of the CB1 receptor protein. In some cases, a CB1 mutation could make you more vulnerable to diseases like anorexia, Crohn’s, or addiction, but in others it could drastically alter your sensitivity to the molecules that bind to it (like THC). This could very well explain why an individual’s sensitivity to cannabis intoxication could be greater or less than the eight other friends sharing the joint.

VID-1163_Infographic_One-in-Seven_withText-1024x576.png


There are also at least seven mutations in the human FAAH gene (an enzyme that breaks down our bodies’ naturally produced cannabinoid molecules), and four mutations in the CB2 receptor. These mutations could have major health implications, and are the subject of intense ongoing research.

But genetic mutations affected by cannabis aren’t restricted to the genes involved in our endogenous cannabinoid system. For example, some people have mutations in the Akt gene (Protein kinase B, not an endocannabinoid-specific gene). This gene can keep cells from dying and inhibit tissue growth and is associated with many types of cancer. People with this mutation are more prone to make errors in judgement and motor responses after consuming cannabis. That’s because the individual’s Akt mutation changes how cannabinoids affect them.

Another important variation outside of the endocannabinoid system is found in the liver. When cannabis is ingested orally (swallowed tincture or edibles), it passes through the digestive system and liver before the cannabinoids can get into the bloodstream and brain. The liver contains many enzymes (again, proteins encoded by our DNA) that process many kinds of medications and substances. One of the more notable enzymes in the liver converts delta-9-THC into 11-hydroxy-THC, which is even more potent at activating the CB1 receptor and inducing intoxication. There are virtually countless individual differences in the efficiency and diversity of liver functions that could affect our experience with edible cannabis.

IMG_2719-2-1024x576.jpg


The genetic mutations that change our experience of cannabis may be present from birth, but they can also occur as a result of our experiences. Genes get turned off and turned on almost constantly throughout our daily lives, in response to many stimuli (invading viruses, diet, stress, you name it). At some point in the near future, it might be possible to do a simple DNA test (swabbing the inside of your cheek) to determine what your genes look like, and what you might be able to expect from using cannabis.
 
I have a friend at the pool I go to that told me she got uncomfortably high (read panic attack and couldn't come down for hours) from a 10mg gummy.... which I found somewhat hilarious. (I know, I know... I'm going to hell :shakehead:) It takes me 100mg in an edible to actually feel high. Now I realize I'm a habitual user and that my tolerance would be much higher than hers. But that is a significant difference and I have to believe that what the article below infers could be at play here.

How Your Genes Influence Your Response to Cannabis

Ever Smoke the Same Flower with a Friend Only to Have Completely Different Experiences? Your Genes Might Have a lot to do with it
So, you’re at a friend’s house, and they hand you a joint. “Be careful,” your friend warns. “This flower is really strong.” You take a drag and next thing you know, you’re feeling … absolutely nothing.

Sound familiar? It illustrates a pretty common occurrence — the same toke exhibiting different effects in different folks — one for which we might have no one to blame but ourselves. Or, more accurately, our own genes.

Cannabis is able to produce a wide array of experiences in human beings. It can make us sleepy, enhance our relationships, change our perception of the world and relieve the symptoms of debilitating diseases. And while different kinds of cannabis products produce different effects, what is even more interesting is that the same cannabis product can produce very different effects among individuals.

IMG_2141-3-1024x576.jpg


For instance, in passing a joint amongst a group of friends, some people may be completely unaffected while others experience intense intoxication of one variety or another. Why is that?

Cannabis exerts its effects through many targets and mechanisms within the brain, most notably the CB1 and CB2 receptors. These receptors are proteins that are made inside of our cells, and like all other proteins our bodies make, the “blueprints” for how to build them reside in our DNA. Although the human genome (the collection of all human genes) is strikingly similar across people, random or inherited edits (mutations) in these blueprints are extremely common. Genetic mutations can often be the source of inherited diseases, and they can also account for some of the differences in people’s reaction to cannabis.

Mutations in the human CB1 receptor (the target for THC and main site of cannabis intoxication) were first observed more than a decade ago. So far, scientists have identified nine variations of this gene in humans. When the blueprints for the protein are different, the function of the protein is almost always affected.

This means that right now, you’re walking around with one of at least nine different versions of the CB1 receptor protein. In some cases, a CB1 mutation could make you more vulnerable to diseases like anorexia, Crohn’s, or addiction, but in others it could drastically alter your sensitivity to the molecules that bind to it (like THC). This could very well explain why an individual’s sensitivity to cannabis intoxication could be greater or less than the eight other friends sharing the joint.

VID-1163_Infographic_One-in-Seven_withText-1024x576.png


There are also at least seven mutations in the human FAAH gene (an enzyme that breaks down our bodies’ naturally produced cannabinoid molecules), and four mutations in the CB2 receptor. These mutations could have major health implications, and are the subject of intense ongoing research.

But genetic mutations affected by cannabis aren’t restricted to the genes involved in our endogenous cannabinoid system. For example, some people have mutations in the Akt gene (Protein kinase B, not an endocannabinoid-specific gene). This gene can keep cells from dying and inhibit tissue growth and is associated with many types of cancer. People with this mutation are more prone to make errors in judgement and motor responses after consuming cannabis. That’s because the individual’s Akt mutation changes how cannabinoids affect them.

Another important variation outside of the endocannabinoid system is found in the liver. When cannabis is ingested orally (swallowed tincture or edibles), it passes through the digestive system and liver before the cannabinoids can get into the bloodstream and brain. The liver contains many enzymes (again, proteins encoded by our DNA) that process many kinds of medications and substances. One of the more notable enzymes in the liver converts delta-9-THC into 11-hydroxy-THC, which is even more potent at activating the CB1 receptor and inducing intoxication. There are virtually countless individual differences in the efficiency and diversity of liver functions that could affect our experience with edible cannabis.

IMG_2719-2-1024x576.jpg


The genetic mutations that change our experience of cannabis may be present from birth, but they can also occur as a result of our experiences. Genes get turned off and turned on almost constantly throughout our daily lives, in response to many stimuli (invading viruses, diet, stress, you name it). At some point in the near future, it might be possible to do a simple DNA test (swabbing the inside of your cheek) to determine what your genes look like, and what you might be able to expect from using cannabis.
hahaha...well, that may be but I'm still betting the difference is just your relative tolerance compared to your friends! haha

Hey @momofthegoons ....maybe you need a 30 day T-break (oh, the horror, the horror!! :yikes: LOL)
 
I though this was an interesting theory on how we all react to cannabis. And it makes sense... two people can consume the same strain and get different results.

I've only quoted the portion of the article that deals with genetics in general. The article continues to talk about the lack of genetics in the Canadian market.


Two sides of the story about cannabis genetics

When we talk about cannabis genetics, a lot of people think about the potency of the plant. But what about you? Do you have the right genes for smoking cannabis?

Cannabis genetics is something that’s been heavily worked and experimented on in the past three decades. It is very rare that we get to see something like herbal genetics being perfected in illegal greenhouses, and yet here we are.

The growers perfected their plants’ genetics by handpicking only the best, strongest and most potent phenotypes and crossed them with their peers. That is how we got extremely potent strains such as OG Kush and many others.

Over the course of the past few years, we’ve seen the rise of CBD-potent strains, such as ACDC, Charlotte’s Web and the Harlequin. These strains grew in popularity as the cannabis market slowly started opening up to the public.

The strain-specific genetics really took off once medical marijuana became legal. It was of utmost importance to know what type of plants you’re growing, otherwise, your whole crop might go to waste.

Genetics are a two-way street
Whether a particular strain of weed will fit your habits and needs doesn’t solely depend on the genetics of that strain. It could have something to do with you as well.

According to John Lem, CEO of Lobo Genetics, if weed doesn’t usually hit you the same way it hits most other people, you maybe have genes that are poorly suited to absorbing and metabolizing cannabinoids.

“Looking into the science, we came to the conclusion that there is actually a genetic basis for someone’s reaction to THC,” said Lem.

Lem’s team looked into three specific genes: CYP2C9, AKT1, and COMT, and created tests that predict how a particular person will respond to a particular cannabis strain. His tests already found their way to several stores in Alberta, even though the wider cannabis and scientific communities have pointed out that further research is required to confirm the results.

Dr. Bernard Le Foll of the Centre for Addiction and Mental Health pointed out that there are many other factors in play, not just the users’ genetic setup.

“The type of environment, the type of previous drug exposure, the dose — that is all very important, possibly more important than genetics,” said Le Foll.

 
Researchers Think They Know Why Weed Makes Some People Happy And Others Paranoid
A new study on rats could help explain why marijuana has different effects on people.


With marijuana now medically legal in 33 states and recreationally legal in 11 states (plus D.C.), the concept of smoking, vaping, or eating it is fair game in the mainstream. But with lingering restrictions on testing it due to the Drug Enforcement Administration, how it affects the brain remains murky territory.

Perhaps nowhere is this more apparent — at least in the recreational realm — than an enduring, unanswered question: Why does marijuana cause one person to experience a pleasurable high, and another to experience paralyzing paranoia?

Thanks to a July 5 study out of Western University in Ontario, Canada, we may be one step closer to an answer. Published in Scientific Reports, the study is one of the few to explore what it deems the “divergent psychological effects” that marijuana’s psychoactive ingredient, tetrahydrocannabinol (THC), produces — and to offer explanations for why this happens.


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HIGHGRADEROOTS VIA GETTY IMAGES
Using rats, the study found evidence that psychological reactions to weed depend on which part of an individual’s brain is most sensitive to THC. If it’s the anterior (front) part of the brain, consuming marijuana will produce rewarding effects (i.e. feelings of ease, reduced anxiety, and joy). If it’s the posterior (back) region that’s most sensitive to THC, it will produce negative reactions (i.e. paranoia and fear).

Steven R. Laviolette, PhD, one of the study’s researchers, tells Yahoo Lifestyle that the study embarked on new territory. “There is not too much known about why there is such differences in response to THC,” Laviolette says. “We know a lot about the longterm and short-term effects...But there is very little known about the specific areas in the brain that are responsible for independently controlling those effects.”

This study, then, is a breakthrough. “It’s a very new finding,” Laviolette tells Yahoo Lifestyle. The multi-year project, led by Christopher Norris, PhD, validates many who have reported experiencing highly negative effects from marijuana. Beyond just negative feelings, the authors found that in severe cases, individuals may experience “schizophrenia-like” symptoms.

The work is a departure from earlier attempts to explain the different psychological reactions, including a 2014 study from Oxford, which suggests that traits such as low self-esteem play a role. Norris and Laviolette’s study suggests instead that the reaction is beyond an individual’s control — and could be based more on genetics. For those who experience a bad reaction, this may be good news.

“Once we figure out what molecular pathways are causing those effects in different areas, then in the longterm we can work on modulating THC formulations so they don’t activate those specific pathways,” Laviolette tells Yahoo Lifestyle. “That’s the really longterm goal of what we’re trying to do here.”

The next step for Laviolette and his colleagues is to attempt to replicate the results in the human brain, which will be no easy task. But for now, he hopes the new research will educate users and help them make informed decisions. “Be aware that we’re starting to unravel some of the more intricate details of how cannabis is affecting the brain,” he tells Yahoo Lifestyle. “Monitor your use and if you’re experiencing negative side effects, talk to your physician.”
 
Sex, drugs and estradiol: why cannabis affects women differently

Frontiers in Behavioral Neuroscience: Females use and experience cannabis differently to males -- and neuroscience is beginning to explain why, says a new review

According to the research, sex hormones help to explain why men and women differ in cannabis use – including prevalence, pattern and reasons for using.
Females use and experience cannabis differently to males — and neuroscience is beginning to explain why, says a new review

— by Matthew Prior, Frontiers science writer

Cannabis use is riding high on a decade-long wave of decriminalization, legalization and unregulated synthetic substitutes. As society examines the impact, an interesting disparity has become apparent: the risks are different in females than in males.

The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity
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A new review of animal studies says that sex differences in response to cannabis are not just socio-cultural, but biological too. Published in Frontiers in Behavioral Neuroscience, it examines the influence of sex hormones like testosterone, estradiol (estrogen) and progesterone on the endocannabinoid system: networks of brain cells which communicate using the same family of chemicals found in cannabis, called ‘cannabinoids’.

Animal studies

“It has been pretty hard to get laboratory animals to self-administer cannabinoids like human cannabis users,” says study co-author Dr Liana Fattore, Senior Researcher at the National Research Council of Italy and President of the Mediterranean Society of Neuroscience. “However, animal studies on the effects of sex hormones and anabolic steroids on cannabinoid self-administration behavior have contributed a lot to our current understanding of sex differences in response to cannabis.”

So how does cannabis affect men and women differently? Besides genetic background and hormonal fluctuations, the paper highlights a number of important sex differences.

Men are up to four times more likely to try cannabis – and use higher doses, more frequently.

“Male sex steroids increase risk-taking behavior and suppress the brain’s reward system, which could explain why males are more likely to try drugs, including cannabis” explains Fattore. “This is true for both natural male sex steroids like testosterone and synthetic steroids like nandrolone.”

But despite lower average cannabis use, women go from first hit to habit faster than men. In fact, men and women differ not only in the prevalence and frequency of cannabis use, pattern and reasons of use, but also in the vulnerability to develop cannabis use disorder.

“Females seem to be more vulnerable, at a neurochemical level, in developing addiction to cannabis,” explains Fattore.

“Studies in rats show that the female hormone estradiol affects control of movement, social behavior and filtering of sensory input to the brain – all targets of drug taking – via modulation of the endocannabinoid system, whose feedback in turn influences estradiol production.

“Specifically, female rats have different levels of endocannabinoids and more sensitive receptors than males in key brain areas related to these functions, with significant changes along the menstrual cycle.

“As a result, the interactions between the endocannabinoid system and the brain level of dopamine – the neurotransmitter of “pleasure” and “reward” – are sex-dependent.”

Human impact

The inconsistency of conditions in these studies greatly complicates interpretation of an already complex role of sex hormones in the endocannabinoid system and cannabinoid sensitivity.

“The effects varied according the specific cannabinoid studied, as well as the strain of animals tested and duration of hormone exposure,” admits Fattore. However, the human data so far are consistent with the idea that estradiol regulates the female response to cannabinoids. As in animals, human males and females are diverse in their genetic and hormonally driven behaviour and they process information differently, perceive emotions in different ways and are differently vulnerable to develop drug addiction.

“Blood levels of enzymes which break down cannabinoids fluctuate across the human menstrual cycle, and imaging studies show that brain levels of cannabinoid receptors increase with aging in females – mirroring in each case changes in estradiol levels.”

Fattore believes that deepening our understanding of the interactions between cannabinoids and sex steroids is crucial in assessing the impact of increasing cannabis use, and tackling the fallout.

“Gender-tailored detoxification treatments and relapse prevention strategies for patients with cannabis addiction are increasingly requested. Optimizing personalized evidence-based prevention and treatment protocols demands further research on the source of sex disparities in cannabis response.”
 

Everything You Know About What Makes Weed Potent May Be Wrong


The answer doesn’t lie in the THC content, like many have believed all these years.


This article originally appeared on VICE India.
You know that one friend who always insists they don’t like smoking weed? A common answer to this pot predicament is usually to justify your friend’s aversion by telling them they just haven’t found the right strain.
For most people, weed with a high THC content, the psychoactive ingredient that dilates time and turns mundane dinners into delicious munchies, is considered a high quality strain. So embedded is this belief that business usually booms for those weed dispensaries (or your local dealer, depending on which part of the world you’re locked down in) that can infuse THC levels over 25 percent. But you may want to put down your glass bong, because a new study is set to shatter your beliefs.

Turns out, you’ve been making one big blunder by assuming stronger is better. A new study published on the JAMA Psychiatry network reveals that THC content has nothing to do with how high your weed will get you. Boom.

This was revealed after researchers at the University of Colorado at Boulder’s Institute of Cognitive Science studied the experiences of 121 cannabis users. Half of the participants were given high THC cannabis concentrates, while the other half preferred blazing buds. Both groups received cannabis at varying “strengths”. While flower users were given buds with 16 percent or 24 percent THC, extract users got oil with 70 to 90 percent THC level. The researchers closely monitored the participants’ blood, moods, and cognitive function. They also examined how intoxicated the participants would feel before, immediately after, and an hour after getting high. This led them to conclude that even though some users were taking in high THC concentrates, it didn’t necessarily get them more high than the other users.

“Surprisingly, we found that potency did not track with intoxication levels,” noted lead author of the study Cinnamon Bidwell, who’s an assistant professor at the Institute of Cognitive Science. “While we saw striking differences in blood levels between the two groups, they were similarly impaired.” In fact, the paper noted that every participant’s self-proclaimed highness and measures of balance and cognitive impairment were the same.

The study also raises concerns about how using cannabis concentrates could put people at a higher risk of long-term side-effects. “It raises a lot of questions about how quickly the body builds up tolerance to cannabis and whether people might be able to achieve desired results at lower doses,” said Bidwell.
These findings fall in line with theories cannabis connoisseurs have been propagating for years: that dabbling with weed goes way beyond THC. With the exception of edibles (which will get you fucked up for longer periods depending on how much weed is involved), other components like cannabidiol or CBD, which is harvested from hemp or marijuana plants that contain less than 0.03 percent THC, also come into play. There are also compounds called terpenes, which affect how cannabis influences your mind and body. All these components of the cannabis plant work together to give you a smooth and seamless high.

Unlike gin or vodka, where alcohol levels define how drunk you’re going to get, how potent your weed is can’t be determined by its THC content. Experts highly recommend that the best way to figure out if you’ve got a good bud is to literally sniff it out. But stopping and smelling the cannabis flowers could potentially be a logistical nightmare, given that medical marijuana dispensaries sell weed in pre-packaged containers. And in countries where weed is still illegal, your dealer probably won’t let you smell the strain before making the money swap.
 

Everything You Know About What Makes Weed Potent May Be Wrong


The answer doesn’t lie in the THC content, like many have believed all these years.


This article originally appeared on VICE India.
You know that one friend who always insists they don’t like smoking weed? A common answer to this pot predicament is usually to justify your friend’s aversion by telling them they just haven’t found the right strain.
For most people, weed with a high THC content, the psychoactive ingredient that dilates time and turns mundane dinners into delicious munchies, is considered a high quality strain. So embedded is this belief that business usually booms for those weed dispensaries (or your local dealer, depending on which part of the world you’re locked down in) that can infuse THC levels over 25 percent. But you may want to put down your glass bong, because a new study is set to shatter your beliefs.

Turns out, you’ve been making one big blunder by assuming stronger is better. A new study published on the JAMA Psychiatry network reveals that THC content has nothing to do with how high your weed will get you. Boom.

This was revealed after researchers at the University of Colorado at Boulder’s Institute of Cognitive Science studied the experiences of 121 cannabis users. Half of the participants were given high THC cannabis concentrates, while the other half preferred blazing buds. Both groups received cannabis at varying “strengths”. While flower users were given buds with 16 percent or 24 percent THC, extract users got oil with 70 to 90 percent THC level. The researchers closely monitored the participants’ blood, moods, and cognitive function. They also examined how intoxicated the participants would feel before, immediately after, and an hour after getting high. This led them to conclude that even though some users were taking in high THC concentrates, it didn’t necessarily get them more high than the other users.

“Surprisingly, we found that potency did not track with intoxication levels,” noted lead author of the study Cinnamon Bidwell, who’s an assistant professor at the Institute of Cognitive Science. “While we saw striking differences in blood levels between the two groups, they were similarly impaired.” In fact, the paper noted that every participant’s self-proclaimed highness and measures of balance and cognitive impairment were the same.

The study also raises concerns about how using cannabis concentrates could put people at a higher risk of long-term side-effects. “It raises a lot of questions about how quickly the body builds up tolerance to cannabis and whether people might be able to achieve desired results at lower doses,” said Bidwell.
These findings fall in line with theories cannabis connoisseurs have been propagating for years: that dabbling with weed goes way beyond THC. With the exception of edibles (which will get you fucked up for longer periods depending on how much weed is involved), other components like cannabidiol or CBD, which is harvested from hemp or marijuana plants that contain less than 0.03 percent THC, also come into play. There are also compounds called terpenes, which affect how cannabis influences your mind and body. All these components of the cannabis plant work together to give you a smooth and seamless high.

Unlike gin or vodka, where alcohol levels define how drunk you’re going to get, how potent your weed is can’t be determined by its THC content. Experts highly recommend that the best way to figure out if you’ve got a good bud is to literally sniff it out. But stopping and smelling the cannabis flowers could potentially be a logistical nightmare, given that medical marijuana dispensaries sell weed in pre-packaged containers. And in countries where weed is still illegal, your dealer probably won’t let you smell the strain before making the money swap.

Iv been aware of this for a while...
When i was in colorado in 2015 i tried loads of high strength (28% ish) flower, but the bet by far was some 15% cheaper one, tasted best and had best high...
I believe terp profile is everything, its why i always grew in soil as it gives better flavour, and therefore a better range of terps...

A dab definitely fucks you up more than flower though... but that contains concentrated terps and other cannabinoids too so thats to be expected..
 

What Effect Does Cannabis Have on Hormones?


Hormones are neurotransmitters. This means that they are chemical messengers which carry instructions to organs and tissues to carry out certain functions. Hormones are produced by various glands in our bodies, with the main hormone-producing gland being the pituitary gland. Hormones are important for a wide range of functions, such as growth, regulating blood sugar levels, the reproductive cycle and mood. The network of glands that secrete these hormones is known as the endocrine system. The endocannabinoid system (ECS) is able to influence various receptor systems in every cell throughout our bodies.

Cannabis affects our hormones. As with many other medications, cannabis can make our bodies produce more hormones or less, depending on whether you are using CBD or THC heavy products. Sometimes, these hormone changes can have a positive medical impact but sometimes the changes can be negative. That’s why it’s important to understand how cannabis affects our hormones. We have touched on how cannabis affects various receptors throughout our bodies. We look at it in a little more detail in this article.

How does Cannabis Affect Our Hormones?​

The ECS is linked to every receptor system in our bodies. Whether it’s dopamine, serotonin or opioid receptors, cannabinoids can “talk” to them and exert their influence in ways both subtle and overt. This includes our hormones and the endocrine system.

However, hormones are complicated, and we do not understand how cannabis and the endocannabinoid system interacts with the endocrine system in any major detail. We do know that cannabis interacts with it, though, as it affects the production of hormones like insulin, testosterone, and estrogen. The effects can be positive or negative.

To give a practical example, with estrogen-positive breast cancer, too much THC may be best avoided, as it can increase estrogen levels. CBD may be a better choice in such an instance, but we shouldn’t necessarily get rid of THC entirely. This is because THC has many cancer-beating properties. Therefore, it is hugely important to match the THC:CBD ratio to the type of cancer you’re treating. But it’s complicated and everybody is different. Here’s what we know so far.

Cannabis and the Hypothalamus-Pituitary-Adrenal (HPA) Axis​


HPA_Axis_Diagram_Brian_M_Sweis_2012.svg.png

HPA Axis Diagram (Brian M Sweis 2012). From Wikimedia Commons. CC BY-SA 3.0. Original work from Jessica Malisch and Theodore Garland. Author: BrianMSweis.


The HPA axis is perhaps one of the most well-known hormonal systems. The HPA is most often associated with flight-or-fight and stress. It is what produces cortisol. Cortisol helps control blood sugar levels, regulates metabolism, reduces inflammation, blood pressure via salt and water regulation, and assists with memory formation.

However, having high levels of cortisol produced by your body can be harmful. The negative feedback loops that prevent too much cortisol from being produced becomes less effective. This is a major problem in those who suffer from post-traumatic stress disorder (PTSD). Both THC and CBD can reduce the amount of cortisol produced by lowering the body’s response to stress.

Too much THC can increase cortisol levels after use so it is important to be careful when using this for some medical conditions. Those who are just starting off using cannabis ought to microdose THC, as small doses can decrease anxiety but large doses can increase anxiety. Microdosing of THC is therefore extremely important to treat anxiety.

Another hormone released by the HPA axis, adrenaline, also has its production lowered by THC use. This dampens the flight-or-fight response. This can lead to slower reactions.

Serotonin is released by the HPA axis, and regulates mood, memory, sleep, digestion and some muscular functions.Low levels of serotonin can cause agitation, migraine, insomnia, and carbohydrate cravings. High levels of serotonin can cause agitation, confusion and sedation. Keeping serotonin levels in balance is very important for the treatment of anxiety, depression and PTSD.

THC helps treat anxiety, PTSD and other associated disorders when used long-term. This is because sustained release of cortisol blunts the stress response and decreases cortisol production.

Long-term THC use blunts the morning spike of cortisol, called Cortisol Awakening Response (CAR), which is one reason why the sleepy effects of THC can be felt upon awakening. This also makes using THC effective for the treatment of insomnia.

CBD can lower the levels of cortisol, but is not necessarily as useful as THC and CBN in treating insomnia.

Cannabis and the Hypothalamus-Pituitary-Thyroid (HPT) Axis​


517px-Thyroid_system.svg.png

Hypothalamus-Pituitary-Thyroid (HPT) Axis homeostasis. Author: Mikael Häggström. From Wikimedia Commons. Public Domain picture.


The HPT axis is responsible for maintaining metabolic rate, heart and digestive functions, muscle control, brain development, and bone health. There are two main hormones released by the thyroid gland: Triiodothyronine (T3) and Thyroxine (T4). The HPT axis is important for controlling the metabolism of our bodies, including the regulation of the body’s internal core temperature, weight, skin and hair.

THC can inhibit TSH. Low circulating TSH levels can lead to symptoms associated with hyperthyroidism, such as fatigue, weight gain, an intolerance to the cold, decreased libido, depression and an abnormal menstrual cycle.

Many of these negatives can be diminished by using cannabinoids like CBD and low doses of tetrahydrocannabivarin (THCV).

It is also worth remembering that reducing TSH levels is not necessarily always a negative. Those suffering from insomnia will want help getting to sleep. Cannabis users generally have a lower body mass index (BMI) compared to non-cannabis users, so weight gain is not usually an issue (although having a low BMI doesn’t mean you aren’t skinny fat, so exercise is key as well). Many find that the stress-relieving properties of cannabis increases their libido. A mixture of THC and CBD at the right dosage may help improve the mood, not cause depression. Some women also find that cannabis is very useful for PMS and menstrual cramps, and there is very little evidence showing that it causes an abnormal menstrual cycle.

Cannabis and the Hypothalamus-Pituitary-Gonadal (HPG) Axis – Cannabis and the Menstrual Cycle​

The HPG axis plays an important role in maintaining the optimal functioning and health of all tissues throughout the body. The HPG axis also oversees the body’s functions related to reproductive health.

THC can reduce hormone levels in the HPG axis, and can lead to a decrease in fertility in both men and women. In women, THC can slow follicle maturation, which can lead to changes in the menstrual cycle. During ovulation, the body releases anandamide, and using THC can cause an excess of endocannabinoid production that disrupts the menstrual cycle.

Now, this may sound frightening to some, but for those suffering from premenstrual syndrome (PMS), using a combination of THC and CBD may reduce pain, cramps and headaches/migraines.

In men, THC has been shown to decrease LH & testosterone, reduce sperm motility, and sperm’s ability to achieve conception. Testosterone is also useful for increasing the mass of muscles and bones and body hair growth. Insufficient testosterone can lead to bone and muscle mass loss.

Interestingly, research has identified that frequent cannabis users have lower levels of prolactin in their blood plasma. Prolactin inhibits FSH and GnRH as well, which is another way in which menstrual cycles and testosterone production are affected.

Cannabis and the Growth Hormone (GH) Axis, aka Insulin-like Growth Factor (IGF-1) Axis​

The GH/IGF axis produces the growth hormone somatotropin, as well as insulin. Somatotropin stimulates growth, cell reproduction, cell regeneration, and in boosting metabolism. Insulin regulates blood-glucose levels by absorbing glucose into the liver, fat and skeletal muscles. The GH axis is also involved in the regulation of brain development, including neurogenesis and neuroprotection.

Cannabis, and in particular cannabinoids like CBD, CBG and THCV, can help improve insulin sensitivity, allowing for sugar to be processed more readily. Cannabis can boost the metabolism, which can prevent weight gain.

THC use when young can affect brain development, and cannabinoids like CBD and THCV have shown to be very useful for the treatment of diabetes and neuropathic pain. For older people, THC, CBD and THCV can be very useful in promoting brain cell growth (neurogenesis).

The ECS is intimately linked with all the hormonal axes, and it is with the GH axis that this link is perhaps most obvious.

Conclusion – The Positives and Negatives of Cannabis Use on Hormones​

Reading the above, it can be tempting to think that cannabis can have a negative effect on hormonal systems. This is not really accurate, as EC dysregulation can cause hormonal dysregulation. This can lead to PMS, migraines, cancer, diabetes, PTSD, anxiety, depression and many more health problems.

Also, much of the focus is on THC. This is because THC binds to and affects CB1 receptors, which can cause changes in hormone levels. Other cannabinoids like CBD have less direct effects, and we know less about how CBD and other cannabinoids affect various hormones. What does seem true is that having a mixture of cannabinoids and terpenes can help mitigate some of the negative effects THC can have on hormones, whilst also retaining some of its benefits.
 

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