Canada is currently in the intersection of two historical social phenomena with massive consequences for public health. Only after decades…
Canada is currently in the intersection of two historical social phenomena with massive consequences for public health.
Only after decades of limiting public access to marijuana, October 17, Canada became the first major industry to fully legalize cannabis for both medical and leisure use.
Secondly, we are in the mood of an aggravated opioid abuse crisis that has already caused thousands of Canadians, young and old deaths.
The interaction between opioids and cannabis has been studied at clinical and pharmacological levels for decades. However, the cannabis potential to modulate the addictive effects of a much more difficult opioid class drug, such as heroin or fentanyl, is only beginning to be investigated.
As a neurologist, I have investigated both the role of brain cannabinoid systems in a variety of neurophysiological processes including schizophrenia, anxiety, cognition and memory and the underlying neurobiological mechanisms responsible for opioid dependence. For many years, we considered that these were largely separate investigative areas.
However, our recent research shows that specific constituents of cannabis can have very profound effects ̵
1; not only modulate the addictive effects of opioids but possibly as treatment for opioid dependence and withdrawal.
In a Complex Plant
Since the early 1960’s, cannabis complexity has gradually been revealed. Cannabis is now known to contain just over 100 different “phytochemicals”, including? -9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
There are also a host of other cannabinoids along with a variety of volatile “terpener” compounds, which give different cannabis strains their distinct aromas and flavors.
Currently, the pharmacology and psychotropic profiles of both THC and CBD are well understood. For example, THC is considered to be the most important psychoactive chemical in marijuana, responsible for its intoxicating effects and rewarding and addictive properties. However, the CBD has been shown to counteract the psychoactive side effects of THC.
As regards their functional effects on the brain, we have shown in rats research that youth exposure to THC can lead to a prolonged hyperactive state of the brain’s dopamine pathways. These are critical to many psychiatric disorders such as schizophrenia and are also partly responsible for opioid’s rewarding and addictive properties.
Other preclinical research has shown that young people’s exposure to THC may increase the sensitivity of the addictive properties of heroin in later life.
Remarkably, the CBD has the exact opposite effect on dopamine. For example, we have shown that CBD can block the sensitization of the brain’s dopamine system in response to drugs such as amphetamine.
Even in the adult brain, we could show that while THC actively activates dopamine, it resembles drugs like morphine
Kappa and mu receptors
Because THC strongly activates dopamine, our first suspicions were the activation of brain cannabinoid receptors can make opioids even more addictive.
But as with all research, history is never so clear. For example, when we entered specific brain areas like prefrontal cortex or amygdala, we found that activation of the cannabinoid receptor system actually made the opioids extremely “aversive” (less addictive) when measured in our rodent models, so they did not produce their beneficial effects.
More surprisingly, when we used drugs to block cannabinoid receptors, they increased the positive effects of opioids.
This means that cannabinoid receptors in these brain circuits acted as a gating mechanism – checking how the brain experienced the rewarding effects of opioids.
We then determined that the cannabinoid receptors in these brain circuits actually controlled opioid dependent signals through two separate receptor mechanisms in the brain. The “kappa” receptor was responsible for making the opioid “mu” receptor capable of making cannabinoids to make the opioids even more addictive.
Long history, drugs like THC that can activate brain cannabinoid receptors can actually reduce the addictive potential of opioid class drugs, especially in some related brain circuits – by regulating how the beneficial and addictive properties of the opioids are treated.
In contrast, the CBD has been shown to strongly inhibit the dopamine pathways of the brain and may have anti-abuse potential. There are already promising data from human clinical trials that indicate that CBD can really serve as a promising treatment for opioid related addictive behaviors.
Cannabis as an Abuse Treatment
It is obvious that the two major constituents of cannabis, THC and CBD can produce dramatically different effects in the brain, especially in brain circuits associated with opioid dependence.
Still important questions remain to be answered. We need to improve our understanding of exactly how the THC and CBD produce their effects.
More importantly, there is an urgent need for early-stage clinical trials to investigate whether and how the THC, CBD or perhaps combinations of both can help alleviate both the beneficial addictive effects of opioids. And if they could turn the addictive adaptations that occur in the brain during the evil cycle of opioid dependence, dependence, recall and relapse.
This article was written by Steven Laviolette, Professor of Institutions of Anatomy and Cell Biology and Psychiatry, Western University. It was originally published on The Conversation, an independent and ideal news source, analysis and comments from academic experts. Enlightenment information is available on the original site. The article is published from the Call under a Creative Commons License