TABLE 1.

Studies of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) to treat patients with mood and anxiety conditions^a

Study	Clinical condition	Type of studyb	Study populationc	Interventiond	Resultse
Masataka, 2019 (30)	Social anxiety disorder	Placebo-controlled, DB RCT	Japanese noncannabis-using teenagers (N=37) in outpatient setting	CBD: 4 weeks of 300 mg qD vs. placebo	Decrease in anxiety: mean±SD FNE score improved more with CBD vs. placebo (24.4±2.7 to 19.1±2.1 vs. 23.5±2. to 23.3±2.9); mean LSAS score improved more with CBD vs. placebo (74.2±7.5 to 62.1±8.7 vs. 69.9±10.3 to 66.8±11.2). Adverse effects were not evaluated.
Bergamaschi et al., 2011 (29)	Social anxiety disorder	Placebo-controlled DB RCT	Portuguese undergraduate students (N=24) undergoing simulated public speaking test in outpatient setting	CBD: single dose of 600 mg vs. placebo	Decrease in anxiety: mean VAMS scores worsened less with CBD vs. placebo (21 vs. 37 points, respectively). Adverse effects were not evaluated.
Fabre and McLendon, 1981 (27)	Psychoneurotic anxiety disorder	Placebo-controlled DB RCT	Psychotropic-free adults (N=20) in private outpatient setting	Nabilone: 28 days of 1 mg TID vs. placebo	Decrease in anxiety: mean HAM-A improved more with nabilone vs. placebo (1.9 to 1.0 vs. 1.7 to 1.7). Adverse effects were common with nabilone (dry mouth, drowsiness).
Glass et al., 1981 (26)	Anxiety neurosis or generalized anxiety disorder	SB, placebo-controlled Latin square	Adults ages 23–30 years (N=8) in outpatient setting	Nabilone: once 2 mg, then weekly .5 −5 mg qD for 5 weeks vs. placebo	No improvement in anxiety as assessed with the POMS. Adverse effects were tachycardia, sedation, and orthostatic hypotension with higher nabilone doses; dizziness, dissociation, and time distortions at ≥4 mg/day.
Crippa et al., 2011 (28)	Social anxiety disorder	Placebo-controlled, DB RCT crossover	Treatment-naïve Portuguese adult men ages 20–33 years (N=10) undergoing anxiety-provoking stimuli in outpatient setting	CBD: single dose of 400 mg vs. placebo	Decrease in anxiety: mean VAMS worsened less with CBD vs. placebo (48.3±7.7 to 30.8±7.7 vs. 46.9±7.6 to 42.1±10.3). Adverse effects were not evaluated or reported.
Jetly et al., 2015 (31)	Nightmares among people with treated PTSD	Placebo-controlled, DB RCT crossover	Canadian male military personnel outpatients (N=10) with PTSD and nightmares refractory to prazosin and antidepressant treatment	Nabilone: 7 weeks of .5–3 mg qD vs. placebo	Improvement in nightmares: change in mean CAPS dream scores indicated greater improvement with nabilone vs. placebo (−3.6±2.4 vs. −1.0±2.1); CGI-C scores improved more with nabilone vs. placebo (1.9±1.1 vs. 3.2±11.2; p=.05). No PTSD scores were reported. Most participants experienced dry mouth and headache.
Ablon and Goodwin, 1974 (33)	Unipolar and bipolar major depression	Placebo-controlled, DB RCT	Adults (N=13) in inpatient setting (NIMH research unit)	THC: 7 days of .3 mg/kg BID vs. placebo	Clinical evaluation revealed no improvement in depressive symptoms. No standardized measures reported. Most participants experienced dysphoric reactions, including panic and psychotic disturbances, even after a single dose.
Kotin et al., 1973 (32)	Unipolar and bipolar major depression	Placebo-controlled, DB RCT crossover	Psychotropic-free adults (N=8) in inpatient setting (NIMH research unit)	THC: 7 days of 5 mg qD to 20 mg BID vs. placebo	Clinical evaluation and 15-item mood checklist (scores not reported) revealed no improvement in depressive symptoms. A 50% attrition rate was reported because of sedation, anxiety, and depersonalization, even after a single dose.

^aStudies are ordered by mental health condition (anxiety, PTSD, and depression).

^bDB, double blind; RCT, randomized controlled trial; SB, single blind.

^cNIMH, National Institute of Mental Health.

^dqD, once a day; TID, three times a day; BID, twice a day.

^eCAPS, Clinician-Administered PTSD Scale (possible scores range from 0 to 4, with higher scores indicating more extreme or incapacitating symptoms); CGI-C, Clinical Global Impression of Change (possible scores range from 1 to 7, with higher scores indicating worse presentation); FNE, Fear of Negative Evaluation Questionnaire (possible scores range from 0 to 30, with higher scores indicating higher levels of social anxiety); HAM-A, Hamilton Anxiety Rating Scale (possible scores range from 0 to 56, with higher scores indicating more severe anxiety); LSAS, Liebowitz Social Anxiety Scale (possible scores range from 0 to 144, with higher scores indicating more severe social anxiety); POMS, Profile of Mood States; VAMS, Visual Analog Mood Scale (this scale has eight specific mood states: afraid, confused, sad, angry, energetic, tired, happy, and tense; possible scores range from 0 to 100 on these mood states, with higher scores indicating higher levels of a specific mood state).