Sativex Did Not Cause Psychiatric Problems or Cognitive Decline in Cannabis-Naive MS Patients

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.

Aragona, Massimiliano et al.·Clinical neuropharmacology·2009·Moderate EvidenceRandomized Controlled Trial
RTHC-00345Randomized Controlled TrialModerate Evidence2009RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Randomized Controlled Trial
Evidence
Moderate Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
No psychiatric or cognitive differences between Sativex and placebo in cannabis-naive MS patients
Evidence Grade:
This is a well-designed crossover RCT, but the very small sample (17) limits statistical power and generalizability.
Study Age:
Published in 2009. Subsequent larger trials have continued to support the psychiatric safety of Sativex at therapeutic doses.
Original Title:
Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study.
Published In:
Clinical neuropharmacology, 32(1), 41-7 (2009)
Database ID:
RTHC-00345

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled TrialGold standard for testing treatments
This study
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Frequently Asked Questions

Is Sativex safe for people who've never used cannabis?

This small study found no psychiatric or cognitive problems in cannabis-naive MS patients using Sativex at therapeutic doses for 3 weeks. However, a correlation between higher THC blood levels and some psychological symptoms suggests dose monitoring may be important.

Could Sativex cause addiction?

This study found no abuse tendencies in 17 patients over 3 weeks. One patient reported increased desire for Sativex after stopping, which resolved. Longer-term addiction risk studies have generally been reassuring for Sativex at therapeutic doses.

Read More on RethinkTHC

Cite This Study

RTHC-00345·https://rethinkthc.com/research/RTHC-00345

APA

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

MLA

Aragona, Massimiliano, et al. "Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study.." Clinical neuropharmacology, 2009. https://doi.org/10.1097/WNF.0B013E3181633497

RethinkTHC

RethinkTHC Research Database. "Psychopathological and cognitive effects of therapeutic cann..." RTHC-00345. Retrieved from https://rethinkthc.com/research/aragona-2009-psychopathological-and-cognitive-effects

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.