Weed hits everyone different but how do opioid receptors affect THC?



Cannabis isn’t for everyone no matter what strain or cannabinoid, topical or gummy you try. Weed can hit everyone with different effects whether the strain is high in THC or CBG, or limonene versus myrcene. Different highs from THC is old news for even occasional consumers but the role that opioid receptors play is unanimously less understood.

A team of researchers hunted for genetic factors that could explain some subjective effects of THC. 70 cannabis consumers with 52 regular users completed a trial and genetic investigation. Funded by Canopy through grants, an opioid receptor was their focal point due to a specific discovery.

Locks and keys with cannabinoids and opioids

Cannabinoid receptors and the entire biological system in all vertebrae are known as locks and ingredients specific to cannabis are one set of keys. So typically, different endocannabinoid tones are the prime suspect behind varying consumer reports for one strain. Subjectivity to a strain’s effect entwines deeper into the body than just the endocannabinoid system, though.

Biological locks of many kinds exist throughout living systems and each opens with a different key. Opioid receptors are not only a prime biological lock, they also alter psychedelic drugs and drive opiate addiction. Interestingly, a Controlled Substances and Cannabis Directorate for Health Canada contributed to the study with peers from the University of Toronto.

Receptor bonds and THC subjectivity

Limited without noting terpenes or the hypothetical entourage effect, the researchers focused on THC and activation of the cannabinoid receptor, CB1. In any case, a specific opioid receptor has a substantial impact on the way the same bud of weed will hit everyone differently.

A bond, known as a heterodimer can be formed between CB1 and opioid receptor, MU1. Dopamine signalling is blocked when MU1 formed this bond, though. Moreover, positive associations with cannabis were markedly reduced when MU1 collaborates with CB1 receptors in mice. Reward responses from cannabis were, therefore, suggested to be driven by CB1 receptors through dopamine signalling. MU1 is one conductor of cannabis’s dance of effects.

Opioid receptor, MU1 moderates the reward response from THC by blocking dopamine. Yet, leaving this as a conclusion completely skips two critical points. A subjective need for increased endocannabinoid tones is one crucial assest, especially anandamide and 2-AG. But there is also the fact that a different cannabinoid receptor, CB2 drives dopamine signalling in the brain’s reward system more than CB1.

Dopamine is one reason weed hits everone different.

A joint, a trial, and a genetic investigation

Rounding things to the researcher’s investigation, for now, 70 consumers abstained from cannabis for two days before smoking a 0.75-gram joint in a controlled and ventilated environment. Cannabis in this Health Canada study used bud with 12.5% THC provided by Aurora.

Trial participants then completed a survey to detail their subjective response to the effect of the joint. A blood sample was collected from each volunteer to analyze THC content, which was added to the genetic investigation and survey. And while specific opioid receptor-producing genes affected the results, some with significance, the study also focused on a cannabis-use disorder (CUD).

Interestingly, the directorate from Health Canada, Bruna Brands, happens to be well-versed in cannabis impairment and driving literature.

CUD versus CED

Let’s go back to the CB2 receptors that Centre for Addiction and Mental Health (CAMH) and UofT researchers missed in this study. Adding to the earlier point about dopamine, CB2 receptors are also known to signal opioid endorphins. And more than one genetic preset is now known to cause a deficient endocannabinoid system. The role that CB2 receptor density plays in subjective cannabis experiences alongside endorphin production deserves an immediate investigation.

The researchers figure that opioid antagonists can help Cannabis Use Disorder but this misinforms the importance of endocannabinoid system deficiencies (CED).

Show your work

  • rs510769 T, a Single Nucleotide Polymorphism had the only positive associations with subjective cannabis use and blood-THC concentrations out of three OPMR1 SNPs investigated.
  • Alongside other COIs, primary researcher, Dr. Le Foll has received medical cannabis from Aurora as a gift as well as a medical donation from Pfizer and Bioprojet.





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