In a crossover trial of 17 MS patients who had never used cannabis, Sativex did not induce psychopathology, impair cognition, or trigger abuse tendencies, though higher blood THC levels correlated with some psychological symptoms.
Read this if you're considering Sativex or other cannabis-based medicines and are concerned about psychiatric side effects.
No psychiatric or cognitive differences between Sativex and placebo in cannabis-naive MS patients
What the researchers found
Seventeen cannabis-naive MS patients were randomized in a double-blind crossover trial to receive Sativex or placebo for 3-week periods, with comprehensive psychological and cognitive assessments.
No significant differences were found between the Sativex and placebo phases on any measured psychological or cognitive variable. Sativex did not cause psychopathology (measured by SCL-90-R), anxiety (Zung scale), cognitive impairment (PASAT), or quality of life changes.
No abuse tendencies or direct withdrawal symptoms were reported. One subject did report increased desire for Sativex with secondary depression after discontinuation.
However, a correlation was found between blood THC levels and scores on interpersonal sensitivity, aggressive behavior, and paranoid tendencies subscales. This suggested that at higher doses than used therapeutically, psychological symptoms might emerge, though the correlation needs confirmation in larger studies.
Why it matters
Safety concerns about psychiatric effects are a major barrier to cannabinoid medicine use. This study in cannabis-naive patients (the most potentially vulnerable group) found Sativex was psychiatrically safe at therapeutic doses, addressing clinician concerns about prescribing cannabinoid medicines.
The numbers in context
17 cannabis-naive MS patients. 3-week crossover design. No significant differences between Sativex and placebo on any psychiatric or cognitive measure. THC blood levels correlated with interpersonal sensitivity, aggression, and paranoid tendency scores.
How the study worked
Eight-week randomized, double-blind, placebo-controlled, parallel-group crossover trial. 17 cannabis-naive MS patients assessed at baseline and after each 3-week treatment phase with SCL-90-R, Self-rating Anxiety Scale, MSFC/PASAT, VAS quality of life, MSIS-29, and Fatigue Severity Scale.
What this study cannot tell us
Very small sample (17 patients). Three-week treatment periods may be too short to detect longer-term psychiatric effects. The THC-symptom correlation was exploratory and needs replication. Cannabis-naive patients may not represent all potential users.
How to read the evidence
This is a well-designed crossover RCT, but the very small sample (17) limits statistical power and generalizability.
When this study was published
Published in 2009. Subsequent larger trials have continued to support the psychiatric safety of Sativex at therapeutic doses.
The bigger picture
This study contributed to the safety evidence supporting Sativex approval. The finding that cannabis-naive patients tolerated the medication without psychiatric problems was particularly reassuring for clinicians considering cannabinoid prescriptions for treatment-naive patients.
Questions still open
- Would longer treatment reveal psychiatric effects? Does the THC-symptom correlation indicate a dose threshold above which psychiatric risk increases? Would cannabis-experienced patients show different patterns?
Common questions
Is Sativex safe for people who've never used cannabis?
Could Sativex cause addiction?
Read the original research
Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study.
Clinical neuropharmacology, 32(1), 41-7
Citation
Aragona, Massimiliano; Onesti, Emanuela; Tomassini, Valentina; Conte, Antonella; Gupta, Shiva; Gilio, Francesca; Pantano, Patrizia; Pozzilli, Carlo; Inghilleri, Maurizio. (2009). Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study.. Clinical neuropharmacology, 32(1), 41-7. https://doi.org/10.1097/WNF.0B013E3181633497
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