Cannabis shows some preliminary promise in the treatment of opioid withdrawal, according to new research published in Drug and Alcohol Dependence. But more controlled studies are need to better understand the proper dose range that provides safe and effective therapy with minimal adverse effects.
When someone stops taking opioids after regular use, their body goes through a period of withdrawal, which can be characterized by a range of symptoms, including nausea, vomiting, diarrhea, anxiety, insomnia, and muscle aches. Cannabis interacts with the endocannabinoid system in the body, which is also involved in the processing of pain and the regulation of mood and anxiety, and may play a role in modulating some of these withdrawal symptoms.
Some states in the U.S. have allowed the use of cannabinoids to treat opioid addiction, but the effectiveness of such treatments are still unclear.
“A growing number of U.S. states are authorizing the medicinal use of cannabinoids to substitute opioid prescriptions,” said study author Joao P. De Aquino, an assistant professor of psychiatry at Yale University School of Medicine. “Further, although basic/animal studies provide support for notion that cannabinoid agonists may alleviate opioid withdrawal, there was a need to systematically summarize and appraise the human evidence and provide insights to inform further research.”
The researchers conducted a systematic review of studies that had investigated participants exposed to cannabis or THC while experiencing opioid withdrawal. Despite the growing interest in using cannabinoids as potential therapeutics, only 11 studies were found that were useful for the research. These studies involved 5,330 people, with 64% being men and 36% being women. Nine of the studies used observational designs and two of the studies used experimental designs.
Six of the observation studies collected data at a single time point and three examined at the association between opioid withdrawal and cannabis use over time.
“Especially among observational studies, there was substantial variability in the methods used to assess opioid withdrawal, which prevented quantitatively synthesizing the data with a meta-analysis,” De Aquino said. “Further, although this is a highly relevant question, only two clinical trials have been conceived to address it thus far.”
The researchers found that the observational studies produced mixed results. Four of them found an association between cannabis exposure and the alleviation of opioid withdrawal, while one suggested that cannabis use made withdrawal worse. The four remaining studies showed no significant effect.
The reason for the different results from the observational studies in this review may be due to differences in the people being studied and how much cannabis they were using. Other factors, such as the type of opioid being used, the daily dose, and how long the treatment lasted, may also play a role. Additionally, THC can have two different effects. While lower doses can help alleviate anxiety, higher doses can increase anxiety and produce physical side effects like a fast heartbeat. These side effects could make quitting opioids worse.
The two experimental studies indicated that THC helped a small to a moderate amount with opioid withdrawal.
“Although there is preliminary human evidence that cannabinoid agonists may alleviate opioid withdrawal, most of the evidence comes from observational studies. Only two clinical trials were designed to examine the withdrawal-alleviating effects of cannabinoid agonists,” De Aquino told PsyPost.
“In these two clinical trials, the withdrawal-alleviating effects of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, were modest — and occurred at the cost of dose-dependent cardiovascular side effects, changes in mood, and addictive potential.”
For example, one experimental study had sought to test the impact of various doses of dronabinol. The treatment produced modest alleviation of subjective and objective opioid withdrawal symptoms. But the researchers discontinued the highest dose (40 mg) after participants experienced persistent tachycardia and heightened anxiety.
De Aquino emphasized that more research is needed to determine whether the benefits of using cannabinoids outweigh the potential side effects.
“This is a complex question with a lot moving parts, so addressing it requires experimental control,” the researcher explained. “For instance, the withdrawal-alleviating effects of cannabinoids may depend on the type of opioid agonist, the baseline levels of opioid and cannabinoid exposure, individual factors, and the type of cannabis and constituent cannabinoid. In summary, more experimental human research is needed to estimate if the risk/benefit ratio of cannabinoids justifies their use to relieve withdrawal among specific clinical populations.”
The study, “Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies“, was authored by Joao P. De Aquino, Anees Bahji, Oscar Gómez, and Mehmet Sofuoglu.