Sativex at High Fixed Doses Reduced Cannabis Withdrawal Symptoms in Dependent Users | Research

The takeaway

In a proof-of-concept trial, high fixed doses of Sativex significantly reduced cannabis withdrawal symptoms during abstinence periods, though self-titrated (lower) doses were less effective.

Read this if you experience withdrawal symptoms when stopping cannabis and are interested in pharmacological support for quitting.

High fixed Sativex doses (up to 108 mg THC/100 mg CBD daily) significantly reduced withdrawal symptoms vs placebo.

What the researchers found

Nine cannabis-dependent community members underwent an 8-week trial alternating between smoking-as-usual periods and cannabis abstinence periods. During abstinence, they received either high fixed doses, self-titrated doses, or placebo of Sativex (up to 108 mg THC / 100 mg CBD daily).

High fixed doses of Sativex were well tolerated and significantly reduced withdrawal symptoms compared to placebo, as measured by both the Cannabis Withdrawal Scale and Marijuana Withdrawal Checklist. However, Sativex did not significantly reduce craving.

When participants self-titrated, they chose lower doses that showed limited efficacy compared to the high fixed doses. Participants also reported a significantly lower "high" from Sativex or placebo compared to their usual cannabis smoking, indicating Sativex did not simply replace the intoxication.

Why it matters

There is currently no approved pharmacological treatment for cannabis dependence. This study provides proof-of-concept that Sativex, at appropriately high doses, can manage withdrawal symptoms, which is often the primary barrier to successful cannabis cessation. The finding that self-titrated doses were insufficient is clinically important for treatment design.

The numbers in context

9 participants. Doses up to 108 mg THC / 100 mg CBD daily. High fixed doses significantly reduced withdrawal. Self-titrated doses were lower and less effective. Craving was not significantly reduced. Participants reported less "high" from Sativex than usual cannabis.

How the study worked

Proof-of-concept, double-blind, placebo-controlled trial using an ABACADAE design (four smoking-as-usual conditions alternating with four abstinence conditions). Nine cannabis-dependent subjects received randomized, counterbalanced doses of Sativex or placebo during abstinence periods. Withdrawal, craving, and subjective effects were measured with validated instruments. Compliance was verified by self-reports, vial weight, and toxicology.

What this study cannot tell us

Very small sample size (9 participants). Proof-of-concept design does not establish efficacy. The alternating design with multiple conditions is complex. The dose of Sativex that worked was high and may raise concerns about simply substituting one cannabinoid product for another. Craving was not reduced, which could limit real-world effectiveness.

How to read the evidence

Preliminary evidence from a very small proof-of-concept trial. The design is rigorous but the sample size severely limits conclusions.

When this study was published

Published in 2016. Pharmacological treatments for cannabis dependence remain an active area of clinical research.

The bigger picture

Cannabis withdrawal is now recognized as a clinical syndrome, but no pharmacotherapy exists for it. Sativex offers a controlled-dose approach to agonist substitution therapy (similar to methadone for opioid dependence). The challenge is that patients naturally choose lower doses when self-titrating, which may be insufficient for symptom relief.

Questions still open

Would a longer trial show sustained benefits? Can the withdrawal relief be maintained during a complete cessation protocol? Would a tapering Sativex regimen lead to successful long-term abstinence? Why did Sativex reduce withdrawal but not craving?

Common questions

Is there medication for cannabis withdrawal?

No approved medication exists yet, but this small study showed that Sativex (THC + CBD spray) at high doses reduced withdrawal symptoms during abstinence. This is a proof-of-concept finding that needs confirmation in larger trials.

Does Sativex just replace one cannabis product with another?

Participants reported significantly less "high" from Sativex compared to their usual cannabis, suggesting it manages withdrawal without reproducing the intoxication. The approach is similar to nicotine patches for cigarette cessation.

Read the original research

Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

Drug and alcohol dependence, 161, 298-306

View on PubMed ↗Publisher’s paper ↗

Citation

Trigo, Jose M; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J; Huestis, Marilyn A; Le Foll, Bernard. (2016). Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.. Drug and alcohol dependence, 161, 298-306. https://doi.org/10.1016/j.drugalcdep.2016.02.020