CNS Drugs

, Volume 32, Issue 12, pp 1113–1129 | Cite as

A Systematic Review of the Efficacy of Cannabinoid Agonist Replacement Therapy for Cannabis Withdrawal Symptoms

  • Maira Aguiar Werneck
  • Guilherme Trevizan Kortas
  • Arthur Guerra de Andrade
  • João Mauricio Castaldelli-MaiaEmail author
Systematic Review



About 30% of regular cannabis users report withdrawal symptoms on cessation of prolonged use, such as irritability, insomnia, decreased appetite, depressed mood, anxiety, and restlessness. However, among highly dependent and/or in-treatment users, the incidence of withdrawal can be even higher, reaching up to 50–95% of individuals. This syndrome was only recognized by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as a diagnosis with specific criteria in 2013. The treatment options are poor, with high rates of relapse and non-responders. In this scenario, agonist replacement therapy with cannabinoids has demonstrated potential as a promising therapeutic intervention, with a series of studies having been carried out in recent years.


This review sought to summarize trials with cannabinoid agonist replacement therapy for cannabis withdrawal symptoms with the aim of evaluating the efficacy of this pharmacological intervention.

Data Sources

We entered the following search terms on the PubMed, Web of Science and PsycINFO databases: (marijuana OR marihuana OR cannabis OR THC OR tetrahydrocannabinol OR hashish OR pot) AND (treatment OR medication) AND (withdrawal OR abstinence) AND (dronabinol OR nabilone OR nabiximols OR sativex OR cesamet OR synthetic cannabinoid). The date of the most recent search was September 2017.

Study Eligibility Criteria, Participants, and Interventions

Original trials, published in English, performed on humans and dealing with cannabis users who were treated for cannabis withdrawal symptoms using synthetic cannabinoids were all included in the present systematic review. Quality and risk of bias across studies were assessed using a Cochrane tool.

Study Appraisal and Synthesis Methods

The first, second, and last authors read the abstracts of all studies found in the search (n = 243). The inclusion and exclusion criteria were applied, and 233 articles were excluded. The first and second authors independently developed a data extraction sheet based on the included articles.


The present review included ten original articles. Despite the limited number of studies and methodological differences, our findings demonstrate that the use of dronabinol, nabilone, or nabiximols, either alone or in combination with other drugs, shows promise in reducing cannabis withdrawal symptoms, probably with a dose-dependent effect. This has also been considered a safe group of medications with good tolerability and few adverse effects.


No method of handling data and combining results of studies was carried out, representing a limitation of the review.

Conclusions and Implication of the Key Findings

Cannabinoids appear to be a promising group of drugs for the treatment of cannabis withdrawal symptoms. These medications may help decrease the rate of relapse in the treatment of cannabis dependence due to withdrawal symptoms occurring within the first few weeks of treatment.

Systematic Review Registration

The protocol for this review has been registered in the PROSPERO International prospective register of systematic reviews (PROSPERO 2014:CRD42014014118).


Compliance with Ethical Standards

Conflict of interest

Dr. Castaldelli-Maia has been awarded a Pfizer Independent Grant for Learning and Change (IGLC) managed by Global Bridges (Healthcare Alliance for Tobacco Dependence Treatment) hosted at the Mayo Clinic, to support free smoking cessation treatment training in addiction/mental health care units in Brazil (Grant IGLC 13513957) and Portugal (Grant IGLC 25629313), which had no relationship with the present study. Dr. A. G. Andrade is Executive President of the Center for Information on Health and Alcohol (CISA), which had no funding relationship with this project. Dr Werneck and Dr Kortas have no conflicts of interest.


There were no funding sources for this article.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Maira Aguiar Werneck
    • 1
    • 2
  • Guilherme Trevizan Kortas
    • 1
  • Arthur Guerra de Andrade
    • 1
    • 2
  • João Mauricio Castaldelli-Maia
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Neuroscience, Medical SchoolFundação do ABCSanto AndréBrazil
  2. 2.Department of Psychiatry, Medical SchoolUniversity of São PauloSão PauloBrazil
  3. 3.ABC Center for Mental Health StudiesSanto AndréBrazil
  4. 4.Departamento de Neurociência da Faculdade de Medicina do ABCSanto AndréBrazil

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