In all users, crude cannabis extracts produce a characteristic high and a tendency for addiction. Raphael Mechoulam, now popularly considered the “Father of Cannabis Science,” designed a series of research models to study the chemical analysis of the cannabis plant. Before this period, plant-derived drugs, including morphine, have been properly studied and characterized. Working on a large consignment of confiscated Moroccan hashish donated by the Israeli Police Department, Mechoulam isolated a few distinct chemical compounds from the cannabis plant. 

Preliminary tests in primates confirmed that THC is the primary compound responsible for the biochemical activity. THC exhibit varied effects ranging from euphoria, paranoia to hyperactivity—this confirmed THC as the psychoactive component in the cannabis plant. Currently, the research into cannabis has since expanded beyond biochemical activity to include cannabis abuse and addiction. Constituent isolation and use in medicine confirmed CBD’s therapeutic benefits with little or no side effects in some patients. Unlike other controlled substances, withdrawal symptoms were not noticed in patients managed with cannabidiol. 

In 2017, a randomized, placebo-controlled, double-blind study was conducted in healthy marijuana users to determine the addictive tendency of oral cannabidiol. The study compared a possible signal for abuse in administered doses of oral cannabidiol and smoked marijuana. As published in the Journal of Drug and Alcohol Dependence, active marijuana reliably produced abuse-related subjective effects; however, CBD displayed no abuse liability signals at the doses tested.


The pharmacology of cannabidiol

As a general rule of thumb, the pharmacology of cannabinoids is complex and involves many receptors, transporters, and enzymes. CBD is a multi-target drug interacting with components of the endocannabinoid system and other non-endocannabinoid signaling systems. Although there are many grey areas about the science of cannabinoids, however, the pharmacology of cannabidiol appears to be dose-dependent. At a low concentration, CBD blocks the nucleoside transporter (ENT) ant the transient receptor potential of the melastatin type 8 (TRPM8) channel. CBD also enhances the 5-HT1a receptor’s effects and the transient receptor potential of ankyrin type 1 (TRPA1). 

At a high concentration, CBD activates the activity of the nuclear peroxisome proliferator-activated receptor and the transient receptor potential of vanilliod type 1 and 2 (TRPV1,2). Unlike THC, CBD does not activate the cannabinoid receptors. Research evidences are suggesting that cannabidiol acts as an inverse agonist at these receptors. The activity of cannabidiol at the cannabinoid receptors explains an important component of its non-addictive property. At these receptors, CBD reduces the psychoactive effects of THC and enhances its tolerability. Some researchers have also provided evidences suggesting that CBD counteracts the activation of CB1 receptors in the brain.


Cannabis addiction and the science of drug dependence

Drug addiction is a complex relapsing disorder spanning different pathological stages—anticipation, intoxication, and withdrawal. These stages set up a cycle of addiction patterns that can be influenced by drug dose and duration of use. The addiction cycle involves an interaction between the neurotransmitters of the brain and the neurocircuits, ultimately leading to drug dependence. 


The endocannabinoid system modulates the primary rewarding effects of drugs of abuse and contributes to the addiction cycle. Chronic administration of drugs of abuse significantly alters the levels of endocannabinoids.  In addiction models studied in animals, consistent results suggest that repeated use of these drugs elevates the endocannabinoid levels in the limbic system and produces structural changes in the brain. Studies have also described the pleasure stimuli initiated by these drug contributes to the addiction cycle and mediates the withdrawal symptoms noticed in patients. 

In humans, withdrawal symptoms are associated with low dopaminergic tone and striatal reactivity to dopaminergic stimulation. Judging from initial findings suggesting that the endocannabinoid system can modulate dopaminergic reward circuits, experts have suggested that the endocannabinoid system plays a significant role in drug addiction. Cannabinoid addiction has been linked with a range of symptoms, including a decrease in psychomotor activity, heightened perception, irresistible impulses, and alterations in cognition. 

In animal models, analgesia, catalepsy, and hypothermia are observed in with cannabis addiction. In 2001, the Archive of General Psychiatry published the study results investigating the link between cannabinoid receptors and symptoms associated with cannabis addiction. This result suggests that CB1 receptors’ activation is primarily responsible for the cannabis high and dependence noticed in users addicted to cannabis.  


Cannabidiol and addiction

The subject of whether CBD use can result in drug dependence and addiction has ignited a series of debates in the medical world. With the advent of medical cannabis, research focus on cannabis safety in patients has also been modified to include studies on possibilities of dependence and addiction with cannabidiol use. However, all research reports available on this subject suggests that unlike THC, CBD does not cause drug dependence in human subjects. Cannabidiol does not activate the cannabinoid receptors and, as such unable to produce a psychoactive effect. 

The pleasure sensation and euphoria created by THC are an integral component needed to modulate the brain’s reward centers. CBD lacks these effects and cannot trigger the dopamine rush considered important in the addiction cycle. This breaks the brain reward-circuit and blocks signals of abuse liability in users. Consequently, cannabidiol use is not associated with drug dependence and symptoms of withdrawal. Interestingly, cannabidiol has shown potential in the management substance in humans. By counteracting THC’s psychoactive properties, cannabidiol is potentially useful in reversing addiction and managing withdrawal symptoms in chronic cannabis users.  



Ian Parkes

Ian has been writing for a number of high growth industries for the past decade. Having plied his trade in the craft beer industry, Ian drew parallels between that and the world of CBD and soon became fascinated. Ian enjoys writing about innovation in the industry, particularly as it relates to the development of the leading brands.

See all posts by Ian Parkes

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