Cannabis Withdrawal: Nabiximols as an Agonist Replacement Therapy

David J. Allsop, PhD National Cannabis Prevention and Information Centre, National Drug and Alcohol Research Centre, Faculty of Medicine Now with the School of Psychology, University of Sydney, Sydney, Interview with:
David J. Allsop, PhD
National Cannabis Prevention and Information Centre, National Drug and Alcohol Research Centre, Faculty of Medicine
Now with the School of Psychology, University of Sydney, Sydney, Australia What are the main findings of the study?

Dr. Allsop: We found that administering a botanical preparation of the cannabinoids Tetrahydrocannabidiol (THC – the main psychoactive ingredient in cannabis) and Cannabidiol (a lesser known component of the cannabis plant that
counteracts the psychotogenic effects of THC with anxiolytic properties) to
dependent cannabis smokers during initial abstinence from cannabis
substantially dampened their withdrawal experience. In essence this is akin
to Nicotine Replacement Therapy (NRT) but for cannabis users. It might seem
obvious – sure you give cannabis users a cannabis preparation and they find
it easier to quit – but this is important because it has never been done
before – and we currently have no consensus evidence based medicines to
offer cannabis users who ask for help.

Beyond dampening their cannabis withdrawal symptoms (irritability, sleep
difficulties, cravings for cannabis etc), we also observed a strong impact
of this new drug on retaining cannabis patients in treatment. Basically
what we found is that 50% of the people on placebo had gone home before the
end of the inpatient detox, whereas 85% of the people receiving the
experimental drug (sativex) were still in treatment at the end. This is a
really important finding as cannabis users, like most other drugs of
dependence, are notoriously difficult to retain in treatment. Having a tool
such as sativex, to keep people coming back to treatment facilities,
enables a greater opportunity to expose people to the other health services
involved in treatment, such as cognitive behavioural therapy delivered by
psychologists. All up, greater retention in treatment should lead to better
treatment outcomes – everyone’s a winner. Were any of the findings unexpected?

Dr. Allsop: We administered the highest dose of sativex that has ever been administered
to humans – delivering some 85mg of THC and about the same amount of CBD in a day, and yet the patients couldn’t tell whether they were on sativex or
placebo! This means that they were not getting intoxicated by the high
doses of cannabinoids that we were delivering (in fact we asked them on a
scale of 0-10 how intoxicated they were after each dose and most were
around 2, and it was not different for the two treatment groups). This is
important information because any criticism of this type of “replacement”
therapy is usually based on the fact that giving psychoactive substances to
patients who are addicted to them could lead to abuse and diversion of the
medication. However in this study we demonstrate that it is highly unlikely
that sativex, with this combination of cannabinoids, would be desirable on
the street or as a substance of abuse in and of itself. To support this, we
also found that people on the cannabinoid drug didn’t suffer any type of
rebound withdrawal from the drug itself when we stopped administering it
and observed them closely for another three days. If people are not getting
stoned from the drug, cannot tell if they are on it or on the placebo, and
don’t suffer any withdrawals – well then there is no reason that it shouldn’t
be accepted by physicians treating people with cannabis dependence. What should clinicians and patients take away from your report?

Dr. Allsop: The take home message is that cannabis withdrawal is a real issue for
dependent cannabis users and can seriously jeopardize a quit attempt.
Cannabis users  however rarely see the link between their crabby mood,
irritability and snappiness, even anger, depression, anxiety, cravings and
sleep difficulties during initial abstinence from cannabis and should be
educated about what to expect when they try to give up. If patients know
that their sleep problems and irritability will pass after 1 to 2 weeks
they might be more inclined to tough it out rather than relapse to cannabis
use. Unfortunately Sativex is a very tightly controlled medicine in most
jurisdictions around the world. Its available to doctors in a small handful
of countries for people with spasticity from multiple sclerosis – but the
guidelines and regulations around its use make it difficult to use for even
that indication. So its unlikely that people will be able to get it for
cannabis dependence in the near future. However we hope that this study
marks the beginning of the process of making people aware of the issue, and
that it highlights to clinicians and policy makers that cannabis dependence
is a major issue that can be better managed with this drug if only it were
available. What recommendations do you have for future research as a result of this study?

Dr. Allsop: This study was pretty unanimous in its findings – Sativex definitely
dampens the experience of cannabis withdrawal and retains people in
treatment for longer. However we did it in an inpatient setting in order to
safely test its appropriateness for this indication. Most cannabis users
wouldn’t want to go into a hospital detox facility for this relatively mild
but persistent (and significant) indication. It would be akin to sending a
cigarette smoker into an inpatient detox unit for their cigarettes. It just
doesn’t happen. So what we need now is to test Sativex out on the street so
to speak. We need to find out whether cannabis treatment seekers in their
home environment are benefited from this drug. Do they actually reduce or
stop smoking cannabis when they have access to it? After that study is done
– if it works – well there is no argument left for not approving this
medication for treating cannabis dependence.


Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal
A Randomized Clinical Trial

Allsop DJ, Copeland J, Lintzeris N, et al. Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial. JAMA Psychiatry. 2014;():. doi:10.1001/jamapsychiatry.2013.3947.


Last Updated on January 21, 2014 by Marie Benz MD FAAD