Multiple sclerosis. According to American Academy of Neurology guidelines, physicians may provide MM as an alternative treatment for patients with MS-related spasticity.33 Multiple studies have tested MM and MM-related extracts for treating spasticity related to MS.34,35 In a placebo-controlled crossover study, Corey-Bloom et al34 reported a significant reduction in spasticity, measured using the modified Ashworth scale, in MS patients receiving Cannabis cigarettes vs placebo cigarettes (P < .0001). However, compared with the placebo group, patients who received MM had significant adverse effects, primarily cognitive impairment (P = .003).
In a multicenter RCT (N = 572 patients with refractory MS spasticity), Novotna et al36 evaluated nabiximols, an oral mucosal spray of a formulated extract of Cannabis that contains THC and CBD in a 1:1 ratio. They assessed spasticity using the Numerical Spasticity Rating Scale (NRS). Results were confirmed by measuring the number of daily spasms, self-report of sleep quality, and activities of daily living. After 4 weeks of single-blind treatment, patients who responded to nabiximols (≥20% improvement in spasticity) were randomized to a placebo group or nabiximols group for 12 additional weeks. After 12 weeks, compared with those who received placebo, those in the nabiximols group experienced a statistically significant reduction in spasticity based on NRS score (P = .0002).
For a summary of evidence on MM for treating glaucoma, Crohn’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, see Box 3.37-43
Box 3
Cannabis for treating glaucoma, Crohn’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis
Glaucoma. In a placebo-controlled study, oromucosal administration of medical marijuana (MM) reduced intraocular pressure from 28 mm Hg to 22 mm Hg, with a duration of action of 3.5 hours.37However, the American Academy of Ophthalmologists does not recommend treating glaucoma with MM because the effect is short-lasting, and MM causes significant cognitive impairment compared with other standardized treatments.38 MM also leads to decreased blood pressure, which lowers blood flow to the optic nerve, thus increasing the risk of blindness.
Crohn’s disease. A randomized controlled trial (RCT) of MM for Crohn’s disease was conducted using the Crohn’s Disease Activity Index (CDAI) to assess for remission. In this 8-week study,21 individuals with Crohn’s disease were administered smoked MM (115 mg of delta-9-tetrahydrocannabinol [THC]) or placebo.39 Eligible patients were at least 20 years old, had active Crohn’s disease (CDAI >200), and had not responded to medical treatment for the illness. Compared with those who received placebo, patients who received MM experienced a statistically significant reduction in CDAI scores (P < .05). However, at follow-up 2 weeks after the study, when MM was no longer administered, there was no difference in mean CDAI scores between the 2 groups. Five of the 11 patients in the MM group achieved clinical remission, compared with 1 of 10 in the placebo group, but this difference was not statistically significant.
Parkinson’s disease (PD). According to the American Academy of Neurology, oral Cannabis extracts are “probably ineffective” for levodopa-induced dyskinesia in patients with PD.40 Reported benefits have come mainly from self-report studies. A 2014 survey (22 patients) found a significant reduction in PD symptoms—mainly relief from drug-induced tremor and pain—when measured using the Unified Parkinson’s Disease Rating Scale (UPDRS). Patients also reported better sleep and reduced pain (measured with a visual analog scale [VAS]). An exploratory double-blind placebo trial (N = 119) found no difference in mean UPDRS and no difference in any neuroprotective measures.41 However, the experimental group had a significantly higher quality of life (QOL; P = .05). A similar double-blind crossover study that included 19 patients found no significant difference in dyskinesia, as measured with the UPDRS, in the group receiving oral Cannabis extract compared with the placebo group.42
Amyotrophic lateral sclerosis (ALS). A randomized double-blind crossover trial of 27 ALS patients found that an oral THC extract (dronabinol, 5 mg, twice daily) had no significant effects on spasticity, as measured with the VAS.43 There was also no significant difference between the experimental and placebo groups on number of spasms (also measured with a VAS), quality of sleep (measured with the Sleep Disorders Questionnaire), or QOL (measured with the Amyotrophic Lateral Sclerosis Assessment questionnaire).
Psychiatric illnesses
Dementia-related behavioral disturbances. A few clinical trials with small sample sizes have found evidence supporting the use of MM compounds for alleviating neuropsychiatric symptoms of patients with dementia. An open-label pilot study of 6 individuals with late-stage dementia who received dronabinol, 2.5 mg/d, for 2 weeks, found a significant reduction (compared with baseline) in nighttime motor activity as measured with an actometer (P < .0028).44 The secondary Neuropsychiatric Inventory (NPI) assessment found reductions in aberrant motor behavior (P = .042), agitation (P = .042), and nighttime behaviors (P = .42).
A 2014 retrospective analysis of 40 inpatients with dementia-related agitation and appetite loss who were treated with dronabinol (mean dosage: 7.03 mg/d) found reductions in all aspects of agitation, including aberrant vocalization, motor agitation, aggressiveness, and treatment resistance, as measured with the Pittsburgh Agitation Scale (P < .0001).45 The study found no significant improvements in appetite, Global Assessment of Functioning mean score, or number of times patients awoke during the night. Adverse effects included sedation and delirium.
A RCT of 50 dementia patients with clinically relevant neuropsychiatric symptoms found no significant difference in mean NPI scores between patients given placebo and those who received nabiximols, 1.5 mg, 3 times daily.46 There were no significant differences found in agitation, QOL, life activities, or caregiver-scored Caregiver Global Impression of Change scale.
In a small RCT, THC was safe and well tolerated in 10 older patients with dementia.47 A 2009 Cochrane review48 concluded that there was no evidence for the efficacy of MM in treating the neuropsychiatric symptoms related to dementia.
PTSD. Preclinical evidence shows that the endocannabinoid system is involved in regulating emotional memory. Evidence also suggests that cannabinoids may facilitate the extinction of aversive memories.49,50
In 2009, New Mexico became the first state to authorize the use of MM for patients with PTSD. In a study of patients applying for the New Mexico Medical Cannabis Program, researchers used the Clinician Administered Posttraumatic Scale (CAPS) to assess PTSD symptoms.51 A retrospective chart review of the first 80 patients evaluated found significant (P < .0001) reductions of several PTSD symptoms, including intrusive memories, distressing dreams, flashbacks, numbing and avoidance, and hyperarousal, in the group using MM vs those not using MM. There also was a significant difference in CAPS total score (P < .0001). Patients reported a 75% reduction in PTSD symptoms while using MM. This study has several limitations: It was a retrospective review, not an RCT, and patients were prescreened and knew before the study began that MM helped their PTSD symptoms.
In another retrospective study, researchers evaluated treatment with nabilone, 0.5 to 6 mg/d, in 104 incarcerated men with various major mental illnesses; most (91%) met criteria for Cannabis dependence.52 They found significant improvements in sleep and PTSD symptoms.
A double-blind RCT evaluated MM in 10 Canadian male soldiers with PTSD who experienced nightmares despite standard medication treatment. Adjunctive nabilone (maximum dose: 3 mg/d) resulted in a reduction in nightmares as measured by the CAPS recurrent distressing dream of the event item score.53
Currently, there are no adequately powered RCTs of MM in a diverse group of PTSD patients. Most studies are open-label, enriched design, and included white male veterans. No well-conducted trials have evaluated patients with noncombat-related PTSD. Most of the relevant literature consists of case reports of Cannabis use by patients with PTSD.
Anxiety disorders.Patients frequently indicate that smoking Cannabis helps relieve their anxiety, although there is no replicated evidence based on double-blind RCTs to support this. However, in rat models CBD has been shown to facilitate extinction of conditioned fear via the endocannabinoid system.54-56 The mechanism of action is not completely understood. CBD has been shown to have antagonistic action at CB1 and CB2 receptors. It may have similar effects on memory extinction and may be an adjunct to exposure therapies for anxiety disorders.
Das et al57 studied the effects of CBD (32 mg) on extinction and consolidation of memory related to contextual fear in 48 individuals. They found that CBD can enhance extinction learning, and suggested it may have potential as an adjunct to extinction-based therapies for anxiety disorders.
Caveats: Adverse effects, lack of RCTs
Cannabis use causes impairment of learning, memory, attention, and working memory. Adolescents are particularly vulnerable to the effects of Cannabis on brain development at a time when synaptic pruning and increased myelination occur. Normal brain development could be disrupted. Some studies have linked Cannabis use to abnormalities in the amygdala, hippocampus, frontal lobe, and cerebellum. From 1995 to 2014, the potency of Cannabis (THC concentration) increased from 4% to 12%.58 This has substantial implications for increased abuse among adolescents and the deleterious effects of Cannabis on the brain.
Heavy Cannabis use impairs motivation and could precipitate psychosis in vulnerable individuals. Cannabis use may be linked to the development of schizophrenia.59
There are no well-conducted RCTs on the efficacy of MM, and adequate safety data are lacking. There is also lack of consensus among qualified experts. There is soft evidence that MM may be helpful in some medical conditions, including but not limited to CINV, neuropathic pain, epilepsy, and MS-related spasticity. Currently, the benefits of using MM do not appear to outweigh the risks.
Bottom Line
Limited evidence suggests medical marijuana (MM) may be beneficial for treating a few medical conditions, including neuropathic pain and chemotherapy-induced nausea and vomiting. There is no clear and convincing evidence MM is beneficial for psychiatric disorders, and Cannabis can impair cognition and attention and may precipitate psychosis. The risk of deleterious effects are greater in adolescents.
Related Resources
- Nguyen DH, Thant TM. Caring for medical marijuana patients who request controlled prescriptions. Current Psychiatry. 2017;16(8):50-51.
- National Institute on Drug Abuse. Marijuana as medicine. https://www.drugabuse.gov/publications/drugfacts/ marijuana-medicine.
Drug Brand Names
Alizapride • Litican, Superan
Chlorpromazine • Thorazine
Domperidone • Motilium
Dronabinol • Marinol, Syndros
Haloperidol • Haldol
Metoclopramide • Reglan
Nabilone • Cesamet
Nabiximols • Sativex
Ondansetron • Zofran, Zuplenz
Prochlorperazine • Compazine
Thiethylperazine • Torecan