Opioid overdose mortality has been rising since 1999. Among 92,000 drug overdose cases, 75% involved an opioid (CDC, 2020). According to Yasmin Hurd (2017), 2.5 million Americans have an opioid disorder. As a result, preventing more opioid overdose deaths and saving this opioid crisis are urgent.
An epidemiological study compared the opioid analgesic opioid overdose morality in the states with medical cannabis laws and the states without such laws from 1999 to 2010 (Bachhuber, et al., 2014). On average, states, where medical cannabis is available, had a 24.8% lower dose mortality. However, we cannot deduce a causal relationship between the implementation of medical cannabis laws and the reduction of opioid overdose mortality.
A review article looked at eleven studies on the alleviation of opioid withdrawal by THC, the major psychoactive component of cannabis, and found mixed results (Aquino, et al., 2022). Among the nine observational studies, four found an association between the alleviation of opioid withdrawal and cannabis exposure, one showed that cannabis use made withdrawal worse, and the four remaining studies suggested no significant effect. The two experimental studies examined the effect of dronabinol, a synthetic version of THC, and found that the withdrawal-alleviating effects were modest and occurred at the cost of dose-dependent cardiovascular side effects. For example, participants reported experiencing “anxiety attacks” and tachycardia after a 40mg dronabinol intake, which raised safety concerns for the use of THC to treat opioid withdrawal (Jicha, et al., 2015).
Aside from the possible therapeutic use of THC in alleviating opioid withdrawal, cannabis might also have implications in preventing opioid relapse. Ren. Y et al. (2009) examined the effect of cannabidiol (CBD), a non-psychoactive ingredient in cannabis, on reducing heroin-seeking behaviors in rats. Researchers first trained rats to self-administer heroin by pressing a lever, and when the drug was delivered, a white conditioned stimulus light would appear above the active lever. During the training phase, rats learned to associate the delivery of heroin with the white stimulus light, and this stimulus became a heroin-associated cue to rats. After the stable heroin intake behavior was established, rats experienced 14 days of drug abstinence and were divided into treatment and control groups. Rats in the treatment group received a 5 mg/kg CBD injection 24 hours before the testing. During the testing session, they were re-exposed to the stimulus light, and no drug would be delivered after they pressed the lever. The result showed the number of lever presses of rats with the CBD injection was significantly lower than that of rats in the control group, indicating CBD inhibited the cue-induced drug-seeking behaviors during the extinction phase. However, when the rats were directly injected with 0.25mg/kg heroin after drug abstinence, CBD did not affect reducing their drug-seeking behaviors.
Rats’ drug-seeking behavior during the extinction phase is similar to humans’ drug reinstatement. During the drug maintenance phase, opioid users might learn to associate using opioids with particular cues, such as needles and white powder, just like how rats associate the delivery of heroin with the white stimulus light. When opioid-dependent people quit using opioids and stay away from the drug for some time, the appearance of opioid-related cues might trigger them to reinstate opioid use. In this case, using CBD might help to reduce the drug-seeking behaviors of these opioid-dependent people, thus preventing relapse. However, if the behaviors are trigged by opioid injections, then CBD would not be effective.
The mechanism of how cannabinoids might alleviate opioid withdrawal is not yet clear. It might be relevant to the interaction between the opiate and endocannabinoid systems. The endocannabinoid system includes two main types of receptors, CB1 and CB2, and studies suggest CB1 antagonism can reduce morphine withdrawal-induced place aversion. (Wills et al., 2014). In conclusion, more research needs to be done to explore the exact mechanism, and more clinical trials need to be conducted to determine whether the benefits of using cannabinoids outweigh the potential side effects.
Bachhuber, M. A., Saloner, B., Cunningham, C. O., & Barry, C. L. (2014). Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA internal medicine, 174(10), 1668–1673. https://doi.org/10.1001/jamainternmed.2014.4005
Ren, Y., Whittard, J., Higuera-Matas, A., Morris, C. V., & Hurd, Y. L. (2009). Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. The Journal of Neuroscience, 29(47), 14764–14769. https://doi.org/10.1523/jneurosci.4291-09.2009
De Aquino, J. P., Bahji, A., Gómez, O., & Sofuoglu, M. (2022). Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies. Drug and Alcohol Dependence, 241, 109702. https://doi.org/10.1016/j.drugalcdep.2022.109702
Jicha, C. J., Lofwall, M. R., Nuzzo, P. A., Babalonis, S., Elayi, S. C., & Walsh, S. L. (2015). Safety of oral dronabinol during opioid withdrawal in humans. Drug and alcohol dependence, 157, 179–183. https://doi.org/10.1016/j.drugalcdep.2015.09.031
Wills, K. L., Vemuri, K., Kalmar, A., Lee, A., Limebeer, C. L., Makriyannis, A., & Parker, L. A. (2014). CB1 antagonism: Interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats. Psychopharmacology, 231(22), 4291–4300. https://doi.org/10.1007/s00213-014-3575-5
Centers for Disease Control and Prevention. (2022, June 2). Death Rate Maps & Graphs. Centers for Disease Control and Prevention. Retrieved April 14, 2023, from https://www.cdc.gov/drugoverdose/deaths/index.html
Deep Dive: The opioid tsunami: Aspen ideas. Aspen Ideas Festival. (n.d.). Retrieved April 14, 2023, from https://www.aspenideas.org/sessions/deep-dive-the-opioid-tsunami
3 thoughts on “Can cannabinoids help reduce opioid withdrawal and dependence?”
I really enjoyed this blog post, specifically how it is short and easy to read. I also think that the imagery helped to break up the different sections of the reading. However, something that confused me was the paragraph on how cannabis might also have implications in preventing opioid relapse. I was a little confused at first how the research that is talked about connected back to preventing opioid relapse. A suggestion I have for the writer is, in the conclusion, I would wrap up more of what was talked about throughout the entire blog post, instead of solely saying that more research needs to be done/further implications. Overall, I think this is a really good blog post and I am now more interested in cannabinoids within the area of science and research.
This article is really interesting because it uses both experiments and observational studies to explore the link between cannabis and withdrawal severity. I am slightly unclear on how opioid-related environmental cues, which may trigger a relapse, can be quelled by the use of cannabis. Wouldn’t these environmental triggers vary between the two drugs? I would also like to know more about how we can balance the negative side effects of cannabis, such as panic attacks and overdependence, with the possible positives. It seems like those dealing with withdrawal already are prone to over-dependence and abuse of substances, so it may be dangerous to expose them to another drug.
So interesting that CBD helps with cue-induced reinstatement but not drug priming-induced reinstatement! I like that you talked about the parallels of the reinstatement model in animals and humans.