THC Alone (Not CBD) Reduced Some Opioid Withdrawal Signs in Monkeys | Research

The takeaway

In morphine-dependent rhesus monkeys, THC at 1.0 mg/kg reduced some behavioral and physiological withdrawal signs, but CBD alone or combined with THC had no effect, and THC was not more effective than the existing medication lofexidine.

Addiction researchers, opioid treatment specialists, cannabinoid pharmacologists

CBD alone or with THC had no effect on opioid withdrawal signs in monkeys

What the researchers found

THC at 1.0 mg/kg decreased unusual tongue movements (a key behavioral sign of opioid withdrawal in monkeys) and heart rate. Lofexidine at 0.32 mg/kg decreased tongue movements, blood pressure, heart rate, and activity. CBD alone (10-17.8 mg/kg) or combined with THC (0.32 mg/kg) had no significant effect on any withdrawal measure.

Why it matters

Cannabinoids have been proposed as treatments for opioid withdrawal, but this study shows CBD did not help and THC was only modestly effective, not outperforming an already available medication. This tempers enthusiasm for cannabis-based opioid withdrawal treatments.

The numbers in context

THC 1.0 mg/kg: decreased tongue movements and heart rate; lofexidine 0.32 mg/kg: decreased tongue movements, blood pressure, heart rate, activity; CBD 10-17.8 mg/kg: no significant effect alone or with THC 0.32 mg/kg; 3 male rhesus monkeys; morphine 3.2 mg/kg BID

How the study worked

Three male rhesus monkeys received escalating morphine doses up to 3.2 mg/kg twice daily for at least 2 weeks. Morphine was then discontinued for 2 days while behavioral signs (tongue movements) and physiological measures (blood pressure, heart rate, temperature, activity) were assessed after THC, CBD, THC+CBD, lofexidine, or vehicle administration.

What this study cannot tell us

Only 3 monkeys (very small sample), only male animals, specific dosing paradigm may not generalize, withdrawal from morphine may differ from withdrawal from other opioids, acute dosing does not address chronic treatment potential

How to read the evidence

Very small animal study (3 monkeys) with limited generalizability; provides important negative data about CBD for opioid withdrawal

When this study was published

Published 2025

The bigger picture

The opioid crisis has driven interest in any potential treatment for withdrawal. While THC showed some benefit, it did not outperform lofexidine (an existing non-opioid medication), and CBD showed no benefit at all, suggesting cannabinoids are unlikely to be a breakthrough for opioid withdrawal management.

Questions still open

Would higher CBD doses produce effects? Does THC help with subjective withdrawal experiences not captured by these measures? Could cannabinoids serve as adjuncts rather than replacements for existing withdrawal medications?

Common questions

Can cannabis help with opioid withdrawal?

In this monkey study, THC modestly reduced some withdrawal signs (abnormal tongue movements and elevated heart rate) but was not more effective than lofexidine, an already available non-opioid medication. CBD had no effect.

Why did CBD not help with opioid withdrawal?

Despite theoretical reasons to expect CBD might help, doses of 10-17.8 mg/kg produced no significant effects on any behavioral or physiological withdrawal measure, whether given alone or combined with THC.

Read the original research

Effects of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and THC:CBD mixtures on behavioral and physiological signs of morphine withdrawal in rhesus monkeys.

The Journal of pharmacology and experimental therapeutics, 392(9), 103671

View on PubMed ↗Publisher’s paper ↗

Citation

Carey, Lawrence M; Galbo-Thomma, Lindsey K; Maguire, David R; France, Charles P. (2025). Effects of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and THC:CBD mixtures on behavioral and physiological signs of morphine withdrawal in rhesus monkeys.. The Journal of pharmacology and experimental therapeutics, 392(9), 103671. https://doi.org/10.1016/j.jpet.2025.103671