Key messages

• It is not clear whether cannabinoids have an effect on insomnia severity or on sleep quality because the certainty of the evidence is very low.
• Cannabinoids may have no effect on sleep conciliation, sleep awakening or behavior during wakefulness, and are probably associated with frequent adverse effects.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found eight systematic reviews [1],[2],[3],[4],[5],[6],[7],[8] that included three primary studies reported in six references [9],[10],[11],[12],[13],[14], of which two correspond to randomized trials, reported in five references [9],[11],[12],[13],[14].

This table and the summary in general are based on the randomized trials, since the observational study did not increase the certainty of the existing evidence, nor did provide relevant additional information.

What types of patients were included*

The first trial [9] included 15 patients with insomnia (diagnostic criterion was not specified). The second trial [11] included 32 patients diagnosed with chronic insomnia, defined as a sleep disturbance according to self-report at least every other night alternately for a minimum of 6 months. Those who fulfilled these criteria were selected within a population of patients with fibromyalgia. In this last trial, a negative urine test for cannabinoids was also required. The average age was 49.5 years and 16% were men.

What types of interventions were included*

The first trial [9] compared cannabidiol at doses of 40, 80 and 160 mg versus nitrazepam 5 mg and versus placebo. The second trial [11] compared the effect of nabilone between 0.5 to 1 mg versus amitriptyline between 10 to 20 mg. All these drugs were administered orally once a day, before going to sleep.

What types of outcomes
were measured

The first trial [9] measured the duration of sleep and the induction of sleep. The second trial [11] measured the results according to the ISI (Insomnia Severity Index) and LSEQ (Leeds Sleep Evaluation Questionnaire) scales. LSEQ evaluates the reconciliation of sleep, quality of sleep, awakening from sleep and behavior during wakefulness.

In addition, the occurrence of adverse effects associated with the use of cannabinoids was evaluated.

The follow-up of the first trial [11] was 6 weeks (2 weeks each period separated by 2 weeks), the second trial [9] did not specify the duration of follow-up, only that it was "acute".

To whom this evidence does and does not apply

• The evidence presented in this summary applies to people with chronic insomnia.
• It is not specified in the systematic reviews if the population of the primary studies was evaluated in ambulatory or hospitalized context, but it seems reasonable to extrapolate the results of this summary to both scenarios.
• The population studied in one of the trials [11] corresponds to patients diagnosed with fibromyalgia in concomitance with insomnia, but the results of this summary could be applicable to patients without fibromyalgia.

• The outcomes presented in the summary of findings table are those considered critical for decision making by the authors of this article.

• It is an intervention that could have no benefits and that has adverse effects, so the risk / benefit balance is not favorable. 

• Commercial formulations of cannabinoids are generally expensive.
• The cost/benefit balance is not favorable, because it is a costly intervention that has no clear benefit and has adverse effects.
• In addition, in many countries the use and commercialization of these drugs is not authorized, so the cost associated with the process of legalization, production, commercialization and inspection is probably substantive.

• Faced with the evidence presented in this summary, most patients and clinicians should lean against the use of cannabinoids in insomnia.
• There is currently a positive perception about the therapeutic effects of cannabinoids, both in the public and in many health professionals, which places additional difficulties in making decisions informed by evidence in this context.

Differences between this summary and other sources

• There is disagreement with some of the systematic reviews identified. The main reason is because of different weight given to the certainty of the evidence and the incorporation of this factor in the conclusions they present. In addition, two of the reviews [6],[7] interpreted the results of one of the primary studies differently [11]. This error was detected in the guideline The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research [15], in which the correct result is shown when mentioning the two systematic reviews in question.
• The conclusions of this summary disagree with one of the main guidelines [15], which indicates there is moderate evidence for the effectiveness of cannabinoids for short-term outcomes in patients with insomnia associated with other conditions. However, they did not consider the imprecision of the results, the risk of bias of the trials or the inconsistency in some outcomes.

• The probability that future evidence changes the conclusions of this summary on the benefits of cannabinoids for insomnia is high due to the associated uncertainty.
• According to the International Clinical Trials Registry Platform of the World Health Organization, there is an ongoing trial [16] which could change the conclusions presented in this summary.
• New systematic reviews could provide clearer conclusions, given the ones identified may not contain all of the evidence and have important limitations. We did not identify ongoing systematic reviews in the PROSPERO database (International prospective register of systematic reviews).