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Meds Tolerance

momofthegoons

Vapor Accessory Addict
Staff member
Why You Build Up Cannabis Tolerance (And How To Fix It)

Have you ever wondered why you have to consume larger and larger quantities of cannabis to feel the effects? Recent research has the answer, and it also has some good news. Cannabis tolerance is, unfortunately, a real thing. However, a 2016 study suggests that the body begins to recover from tolerance within just a couple days after abstaining.

What is cannabis tolerance?

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Almost every cannabis consumer has experienced this situation: you start off with a small hit of cannabis, and a week later you realize that you need to consume more of it to feel the effects.

Humans develop tolerance to cannabis quite quickly, meaning that consumers become desensitized to the overall effects of the herb over a short period of time.

Interestingly, certain areas of the body develop tolerance more rapidly than others. The colon, for example. One 2009 rodent study found that some functions in the gastrointestinal tract seem to be particularly resistant to tolerance.

In this case, cannabis seemed to slow down the passage of food from the stomach to the small intestine, regardless of other signs of tolerance.

Study explains why you build tolerance

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A study published early last year [2016] in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.explains why cannabis tolerance happens.

The cannabis plant has psychoactive potential because of special chemicals it creates, called phytocannabinoids. These organic chemicals directly engage with special cell receptors in the body, called cannabinoid receptors.

In the brain, the most abundant cannabinoid receptor is the CB1 receptor. The primary psychoactive in the herb, tetrahydrocannabinol (THC), engages this receptor.

While the exact ways THC affects the brain are unknown, it is known that the cannabinoid interacts with the brain in areas that control the following and more:

  • Mood
  • Memory
  • Movement
  • Sleep
  • Reward
Earlier research has found that chronic THC treatment decreases the amount of CB1 receptors expressed in a cell. In the science world, this is called downregulation.

Cells will either upregulate or downregulate various receptors depending on the internal environment of the body. In the case of THC, the downregulation of CB1 receptors leads to tolerance.

Cannabis tolerance doesn’t stick

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The 2016 study confirmed that research. Using positron emission tomography (PET scan) and a special injection of a radioactive material, the researchers were able to get a visual sense of the density of the CB1 receptors in the brain.

The study compared 11 subjects diagnosed with cannabis dependence to 19 volunteers. The images showed that chronic cannabis consumers did, indeed, show lower receptor density. This is an important signifier of tolerance. They then performed these scans again, testing participants during a period of abstinence.

This where the results get interesting. According to the study,

[CB1 downregulation] begins to reverse surprisingly rapidly upon termination of cannabis use and may continue to increase over time.

Amazingly, cannabis tolerance begins to reverse within two days after abstaining from the herb. At the 28-day mark, tolerance continued to improve. This is valuable information for medical cannabis patients, as this means dosage will change should they stop and start their treatment again.

Though cannabinoid receptors start to spring back just a couple of days after abstaining, the density of CB1 receptors in cannabis consuming participants was still lower than the healthy controls at the four-week mark. Though, should participants continue to abstain, things are predicted to catch up to “normal”.

Tolerance breaks

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Many cannabis regulars take tolerance breaks to maintain efficacy with the herb. A tolerance break is a short period of abstinence from the herb. As this study suggests, a mere two days of abstinence seems to be enough to kickstart the upregulation process.

Medical cannabis patients should always work with a health care provider before making major changes to a treatment plan. However, casual cannabis consumers may have a few T-break tricks at their fingers.

Here are three tips for hacking cannabis tolerance:

1. Microdose

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Want to kick your tolerance without much disruption? Start consuming smaller and smaller amounts of cannabis. “Microdosing”, or consuming a very small amount of a substance on a continuous basis, is becoming more popular.

Cannabis tolerance happens when larger and larger amounts of the herb are needed to produce an effect. Switching back to small doses of the plant will not likely be as effective as abstaining. However, it’s a decent compromise for a complete break.

2. Switch to cannabidiol (CBD)

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Both psychoactive THC and nonpsychoactive cannabidiol (CBD) engage the endocannabinoid system. However, these two compounds work in fundamentally different ways. For some, switching to CBD may provide a nice alternative for THC.

Opting for a high-CBD, low-THC strain may be helpful to those looking to stay away from psychoactive cannabis, but still want some of the relaxing and pain-fighting benefits of the herb.

For more information on cycling between cannabinoids, take a look at the full article here.

3. Essential fatty acids

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Omega-3 fatty acid supplementation may also be beneficial when weaning off the cannabis plant. As the body’s own endocannabinoids (the human version of THC) are derived and regulated by from fatty acids. However, there is no research testing the impact of essential fatty acid supplements for cannabis tolerance.

Some research suggests that the probiotic, lactobacillus acidophilus, also increases cannabinoid receptor expression in the gut. Though, there is no research that examines the effects of probiotic supplementation on cannabis tolerance, either.
 

momofthegoons

Vapor Accessory Addict
Staff member
My tolerance is pretty high and I've often wondered if this was a bad thing and have tried multiple times to lower it. Found this article today and maybe it's not such a bad thing...... And this consultant advises keeping a journal of your usage. The last time I went in to re-up my license, my consulting doctor advised the same thing. I think I might start one.


Don’t Knock a Strong Pot Tolerance, It Could Help You Heal

Cannabis tolerance — the gradual acclimation to the sensory impacts of use — is usually framed in a negative light; something to be avoided or remedied. But being able to handle larger doses of cannabinoids can actually mean increased medical benefits.
Cannabis has a bad reputation when it comes to building up tolerance. Countless articles describe the problem: you start using cannabis and it works great, but after a few weeks you find you need more. You increase your dose, only to soon find that this new dose is also insufficient — it just doesn’t get you ‘high’ the same way.


The prescription for this problem is usually to go on a tolerance break, a few weeks where you stop using cannabis and let your system reset. When you go back to using cannabis again, your tolerance will be back down to where you started. The message being communicated is clear: tolerance isn’t something you want to have.

But developing a cannabis tolerance isn’t all bad. For many, especially medical patients, it is a crucial factor in their cannabis use. Many medical patients starting cannabis worry about side effects like difficulty thinking, problems with memory or lack of coordination. One of the great benefits of developing a tolerance to cannabis is that many of these side effects go away: Studies show chronic cannabis users do not suffer from the same disorienting effects that leave occasional users unable to do everyday tasks, such as driving).

I saw this firsthand as a cannabis patient. For me, cannabis was always disorienting. It wasn’t a bad thing, but it did make it impossible to get much done while under the influence.

I remember marveling at a close friend and classmate who could smoke throughout the day while remaining completely normal. He would go to class, have complex conversations about analytic philosophy, work on his doctorate — all while using cannabis.

When I asked him about it he explained that he had a high tolerance. He was just used it.

At that time, I was dealing with intense chronic pain and missing a lot of school and work due to these struggles. Cannabis helped, but I was only using it at night, when I didn’t have any work to do. It was like a time-out from the pain, but it didn’t help me with the real problem — my inability to work when I was in pain.

My friend suggested something that ran counter to everything I had read — I should build up my tolerance.

“Smoke right before you write that paper” he suggested. “It will be weird for a few days, but then you’ll be used to it”.

To my surprise, he was right. Within a week of starting to use cannabis during my regular work and school activities, I was no longer feeling the disorienting side effects. I was free. While I still got relief from my pain and anxiety, I was thinking clearly and felt… normal.

While I worried my tolerance building would lead to continual increases in use, at a certain point my tolerance increases seemed to plateau: I have been on a relatively stable dose for the last five years. If I use the same strain of cannabis for too long, I develop a tolerance to that strain and need to switch it up to keep getting relief. Otherwise I haven’t experienced any tolerance-related problems and always avoid taking tolerance breaks now.

While tolerance breaks are fantastic for recreational users or those with occasional medical needs, I never suggest them for medical patients who have chronic issues they are managing. Just like you would be unlikely to have a doctor suggest you take a few weeks off from an antidepressant or a heart medication, if you are using cannabis for daily medical needs, interrupting this can be disruptive and confusing for your body. And of course, any symptoms you were managing will no longer be getting the help they need.

Still, last summer, I was forced to take a tolerance break: I got a lung infection (unrelated to the cannabis) which was aggravated by smoke, so I spent months unable to use my medicine.

When I started to smoke again a few months later, my tolerance was back at its starting point and I experienced tolerance free cannabis use again. I was totally useless! So, I spent the next few weeks building my tolerance back up. Only then was I able to again use cannabis effectively as medicine.

I thought I might be able to use a lower dose after such a long break, but I quickly found myself back at that stable dose I had been using for years. For all the discomfort of the break, it turned out that I did best on the dose I had already been on.

While tolerance breaks are great for some (and there are certainly medical and recreational users alike who swear by them), for others developing and keeping a certain level of tolerance may be the better route. This can vary drastically from person to person based on their needs and biochemistry.

As a patient consultant, I often work with clients to track their cannabis experiences in a journal. Looking back over a few weeks of entries, many of them are able to better understand what is working for them and what isn’t.
 

momofthegoons

Vapor Accessory Addict
Staff member
Know Your Medicine: Tolerance and Reverse Tolerance

BY BONNI GOLDSTEIN, M.D. ON AUGUST 11TH, 2017

The concept of cannabis tolerance is quite interesting. Now that patients are using preparations that contain different prominent cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabinol (CBN), the question of tolerance no longer relates to THC only.

Tolerance is defined as the need to use more of a drug to get the desired effect. Stated another way, less of an effect is achieved with a previously effective amount. It is clear that tolerance to THC develops following repeated exposure. How much exposure is needed to develop tolerance appears to be different for each person. Animal research in the 1990s suggested that tolerance developed due to a reduction of cannabinoid receptors in the brain after they were exposed to chronic THC.

A 2012 study in humans found the same results, namely that chronic, heavy users of THC-rich cannabis had a decreased number of cannabinoid receptors when compared to non-users. The same study also showed that a 4-week abstinence from THC resulted in an increased number of receptors, revealing that tolerance to THC is reversible. Interestingly, the researchers in this study also reported that different parts of the brain became tolerant at different rates. For instance, one may be using THC to treat pain and anxiety and may find with chronic, heavy use that the anxiety is lessened but the effects on pain relief are lost. Tolerance to the effects of THC is easy to reverse with either abstinence or significant reduction of dosing for a few days. The vast majority of THC users do not experience withdrawal symptoms, however, if this does occur, CBD-rich cannabis can counteract most discomfort.

Cannabidiol (CBD) does not cause tolerance as it does not work by binding to the cannabinoid receptor the same way that THC does. On occasion, some of my patients have reported getting beneficial therapeutic results with CBD who then report that they think they have developed tolerance. However, upon further questioning, most had started a new preparation at the time when the effects were lost. What they interpret as tolerance is likely not; it is much more likely, given the lack of standardization in the production of most CBD preparations, that the product was different in potency or strain and was not delivering the same beneficial effect.

Clinically, it appears that THCA and CBDA, the cannabinoids found in the raw (unheated) flower, do not cause tolerance. Similarly, CBN does not appear to cause tolerance although there has been no research focused on this property.

Reverse tolerance, also called drug sensitization, means that less drug is needed to get the desired effect. This is the opposite of tolerance. One example of reverse tolerance is when an alcoholic becomes intoxicated from a smaller amount of alcohol due to liver damage from chronic use. Reverse tolerance has been described for alcohol, stimulants, opiates, nicotine, and antidepressants. Reverse tolerance does not occur in the majority of people using these substances and likely reflects genetic differences in how one absorbs and metabolizes drugs.

In a 1981 study that looked at cannabinoids as potential antiepileptics, animals developed tolerance to THC in all of the seizure models tested. In contrast, CBD showed evidence of reverse tolerance, meaning the seizures were effectively treated with lower doses over the three weeks of treatment. Quite interestingly, there are dozens of reports of reverse tolerance by parents of children with epilepsy who have been using CBD successfully to reduce seizures.

A number of my pediatric patients who were responding positively to CBD oil for a number of months were reported by the parents to have increased frequency of seizures without the presence of a known trigger (such as the reduction of an antiepileptic drug or signs of an illness, both variables known to trigger seizures). Suspecting reverse tolerance, or “CBD saturation” as this phenomenon is known colloquially, I recommended that the patient skip a few doses and restart at a lower dose, which resolved the issue. Not everyone using CBD experiences reverse tolerance.

Research looking at the mechanisms of action for reverse tolerance for substances other than CBD suggests that various non-cannabinoid receptors, including GABA receptors and NMDA receptors, are likely involved. CBD is also known to interact with these receptors. Another hypothesis of the mechanism of action for CBD reverse tolerance is that CBD enhances endocannabinoid function leading to less CBD needed over time. Likely multiple and overlapping mechanisms of action are contributing to this phenomenon.

Although my clinical experience with “CBD reverse tolerance” is mainly in children with epilepsy, some adult patients report that after a few months on CBD with desired results, they find that they don’t need as much and decrease the dose without the loss of beneficial effects.

Tolerance and reverse tolerance are concepts that all cannabis patients should understand. Knowing your medicine and the possibility that you may need to adjust dosing due to these possibilities will help you troubleshoot your medication regimen if you lose the desired effects.

Sources:

Oviedo, A., et al. Chronic Cannabinoid Administration Alters Cannabinoid Receptor Binding in Rat Brain: A Quantitative Autoradiographic Study. Brain Research (1993) 616: 293-302.

Fan, F., et al. Cannabinoid Down-regulation without Alteration of the Inhibitory Effect of CP 55,940 on Adenyl Cyclase IN the Cerebellum of CP 55,940-tolerant Mice. Brain Research (1996) 706: 13-20 1996.

Hirvonen, Jussi, et al. “Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers.” Molecular psychiatry 17.6 (2012): 642-649.

Vermersch, Patrick. “Sativex® (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data.” Expert review of neurotherapeutics 11.sup4 (2011): 15-19.

Karler, Ralph, and Stuart A. Turkanis. “The cannabinoids as potential antiepileptics.” The Journal of Clinical Pharmacology 21.S1 (1981).

Karler, R., et al. “Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801.” Life sciences 45.7 (1989): 599-606.

Camarini, Rosana, et al. “MK‐801 Blocks the Development of Behavioral Sensitization to Ethanol.” Alcoholism: Clinical and Experimental Research 24.3 (2000): 285-290.

Woo, Sang-Hee, et al. “Inhibition of baclofen on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity.” Pharmacological research 43.4 (2001): 335-340
 

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