Why Cannabis Affects Different People Differently

Whether a person has an enjoyable experience or has adverse effects from cannabis may be determined by which region of the brain it is acting on, according to researchers at the University of Western Ontario.

The psychological effects of marijuana can differ between individuals: some experience highly rewarding effects which may lead to dependence on the drug, while others may experience paranoia, cognitive problems or an increased risk of developing schizophrenia.

“Until now, it was unknown which specific regions of the brain were responsible for these highly divergent effects of marijuana. Translational rodent research performed in our lab has identified highly specific target regions in the brain that seem to independently control the rewarding, addictive properties of marijuana versus the negative psychiatric side-effects associated with its use,”

said Steven Laviolette Ph.D., Professor at Western’s Schulich School of Medicine & Dentistry.

Bivalent Rewarding And Aversive Affective States

By looking at the effect of tetrahydrocannabinol (THC) on a rat brain, the researchers showed that THC, the main psychoactive compound in marijuana, can produce highly rewarding effects in the front-most part of a region of the brain called the nucleus accumbens.

The study showed that THC in this brain area not only produced highly rewarding effects in and of itself, it amplified the addictive properties of opioid drugs like morphine and increased reward-related activity patterns in the neurons.

Effects of ICV THC and CYP on anterior NASh medium spiny neurons activity patterns.
Effects of ICV THC and CYP on anterior NASh medium spiny neurons activity patterns.
Credit: Christopher Norris et al. CC-BY

In contrast, THC in the posterior area of the nucleus accumbens region produced highly adverse effects.

These included more schizophrenia-related cognitive and emotional symptoms and patterns of neuron activity similar to those found in people with schizophrenia.

Genetic Variation

Neuronal recordings demonstrated that THC decreased medium spiny neuron (MSN) activity in the anterior nucleus accumbens and increased the power of gamma (γ) oscillations.

THC increased MSN activity states in the posterior NA medial shell subregion, which is linked to motivational salience, the processing of emotional stimuli, reinforcement, and addiction.

“These findings are important because they suggest why some people have a very positive experience with marijuana when others have a very negative experience. Our data indicate that because the reward and aversion are produced by anatomically distinct areas, the different effects between individuals is likely due to genetic variation leading to differential sensitivity of each area,”

said Norris.

The work was supported by the Canadian Institute of Health Research, the Natural Science and Engineering Research Council of Canada, MITACs and the J&J Memorial Tournament.

Christopher Norris, Hanna J. Szkudlarek, Brian Pereira, Walter Rushlow & Steven R. Laviolette
The Bivalent Rewarding and Aversive properties of Δ9-tetrahydrocannabinol are Mediated Through Dissociable Opioid Receptor Substrates and Neuronal Modulation Mechanisms in Distinct Striatal Sub-Regions
Scientific Reports, volume 9, Article number: 9760 (2019)

A. Douglas Kinghorn (Editor), Heinz Falk (Editor), Simon Gibbons (Editor), Jun’ichi Kobayashi (Editor)
Phytocannabinoids: Unraveling the Complex Chemistry and Pharmacology of Cannabis sativa
Springer; ISBN: 978-3319455396


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