. 2021 Mar;19(3):402–432. doi: 10.2174/1570159X18666200420085712

Table 7.

Experimental studies: reported side effects from cannabinoids.

Author, Year	Inclusion Criteria	Exclusion Criteria			Intervention	Comparison	Side Effects
Randomized Control Trials (Mixed Samples)
Karst et al., 2003 [56]	Neuropathic and somatic pain for >6mo, stable levels of pain medications for >2mo. Aged 18-65y. Consent to participate in study and follow study procedures	No N-methyl-D-aspartate receptor antagonist and cannabinoid concomitant pain-relieving medications. Severe organic or psychiatric disease, pregnancy/attempting to conceive, lactation, use of any investigational drug within 30d prior to first dose of study drug, non-German speaking			CT-3 (10.0mg–max 80.0mg) f/u: 3, 8 hrs	Placebo	↑ Fatigue^f; ↑ Dry mouth^f ; ↑ Limited power of concentration^f; ↑ Pain^f; = Objective concentration; = Vitals (RR, HR, BP, wt, temp, ECG, hematologic and blood chemistry)
Wade et al., 2003 [58]	Neurologic diagnosis and be able to identify troublesome symptoms which were stable and unresponsive to standard treatments	History of drug or alcohol abuse, serious psychiatric illness (excluding depression associated with neurological condition), serious cardiovascular disease or active epilepsy			CBD-rich sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks	Placebo (Inert Plant Material)	= Objective concentration; = Bladder function; = Daily functioning
					THC-rich sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks	Placebo (Inert Plant Material)	↓ Objective Concentration (SOMC) ^j; ↑ Appetite (daily VAS) ^j; = Bladder function; = Daily functioning
					1:1 THC:CBD sublingual spray (2.5mg–max 120mg/d) f/u: 2 wks	Placebo (Inert Plant Material)	= Objective concentration; = Bladder function; = Daily functioning; ↑ Sleep (daily VAS) ^j
Hagenbach et al., 2007 [55] *RCT phase	Terminated taking all spasmolytic medication >3 half-life periods before enrolling, free of illegal drugs. Spasticity without any spasmolytic treatment had to be >3points on the MAS in at least one muscle group	Pregnant, severe somatic and known psychiatric diseases			Dronabinol capsule oral (2.5mg, 5.0mg, 10.0mg) f/u: 1, 8, 43d	Placebo (sesame oil)	↑ Reaction Time; = Vitals (HR, BP, ECG, hematologic and blood chemistry); = Mood; = Functional independence
*Non-RCT phase					Dronabinol capsule oral (2.5mg, 5.0mg, 10.0mg) f/u: 1, 8, 43d	Baseline	↓ Systolic BP; ↑ Vital capacity (43d) ^g; = Mood; = Functional independence; = objective concentration; = Bladder function; ↑ Fatigue (36%); ↑ Dry mouth (32%); ↑ Anxiety (32%); ↑ Disturbance of attention (27%); ↑ Pain (23%); ↑ Dizziness (23%)
*Non-RCT phase					Rectal THC (5.0mg, 10.0mg) f/u: 1, 8, 43d	Baseline	↑MCC (43d) ^k; = Vitals (HR, BP, ECG, hematologic and blood chemistry); = Mood; = Functional independence
Wilsey et al., 2008 [59]	Adults with complex regional pain syndrome (CRPS type 1), SCI, peripheral neuropathy, or nerve injury. Previous cannabis exposure. Must refrain from smoking cannabis or taking oral synthetic delta-9-THC medications for 30d before study session	Candidates who met the criteria for severe major depressive disorder, or candidates with a history or diagnosis of schizophrenia or bipolar depression. Uncontrolled hypertension, cardiovascular disease, chronic pulmonary disease (asthma, chronic pulmonary obstructive disease), active substance abuse			3.5% delta 9-THC cigarettes (9 puffs) f/u: 1, 2, 3, 4, 5, 6 hrs	Placebo	↑ “Feeling high”^j; ↑ “Feeling stoned”^j; ↑ “Impaired”^d; ↑ Sedation^d; ↑ Hunger^b; ↓ Attention; ↓ Learning/memory; ↓ Psychomotor speed; ↑ “Good drug effect”^b; ↑ Calmnessⁱ
Wilsey et al., 2008 [59]					7% delta 9-THC cigarettes (9 puffs) f/u: 1, 2, 3, 4, 5, 6 hrs	Placebo	↑ “Feeling high”^b; ↑ “Feeling stoned”^c; ↑ “Bad drug effect”^d; ↑ “Impaired”^d; ↑ Sedation^e; ↑ Hunger^e; ↓ Learning/memory; ↑ “Good drug effect”^e; ↑ HR (immediately); = Mood; = Spasticity ; = Neurocognition (overall)
Pooyania et al., 2010 [77]	Aged 18-65 with a level of injury at C5 or below, and injury occurred more than 1 year previously. Stable neurologic level, with moderate spasticity (>3 AS). Spasticity medications had to be unchanged for at least 30 days before inclusion and no botulinum toxin injections >4mo	History of heart disease, psychotic disorders, schizophrenia, or any active psychologic disorder. Previous documented sensitivity to marijuana or other cannabinoid agents, severe liver dysfunction, cognitive impairment, a major illness in another body area, fixed tendon contractures. Pregnant or nursing. History of drug dependency, smoked cannabis <30d before study onset, or unwilling to not smoke during the study			Nabilone (0.5mg-1.0mg/d) f/u: 4wks	Placebo	↑ Drowsiness (27.2%); ↑ Dry mouth (18.1%); ↑ Asthenia (18.1%); ↑ Vertigo (18.1%)
Author, Year	Inclusion Criteria		Exclusion Criteria	Intervention		Comparison	Side Effects
Randomized Control Trials (Mixed Samples)
Rintala et al., 2010 [57]	Adults who had sustained an SCI >12 before study entry and who reported chronic (>6mo) neuropathic pain, the intensity of which was rated as >5 at its worst on a scale of 0-10		Previous adverse reaction to any cannabinoid or sesame oil, current or history substance abuse, serious psychological or psychiatric disorder, renal or hepatic insufficiency, history of tachycardia, pregnant or nursing	Dronabinol (5.0mg–max 20.0mg) f/u: 2, 4 wks		Placebo (diphenhydramine)	↑ Constipation; ↑ Fatigue; ↑ Dry mouth; ↑ Abdominal discomfort
Wilsey et al., 2016 [60]	Age 18-70, with pain intensity >4/10, who attend the UC Davis Medical Center Spinal Cord Injury Clinic		Diagnosis of bipolar depression, schizophrenia, severe depression, or affirmation to the statements “I felt life was not worth living”; “I felt like hurting myself”; “I felt like killing myself”. A history of coronary artery disease, obstructive pulmonary disease, severe liver disease, impaired renal function. Current substance use disorder.	2.9% delta 9-THC vaporized cannabis (4-8 puffs) f/u: 60, 120, 180, 240, 300, 360, 420min		Placebo	↑ “Good Drug Effect”^a; ↑ “Bad Drug Effect”^a; ↑ High^a; ↑ Drunk^a; ↑ Stoned^a; ↑ Sedated^a; ↑ Nausea^a; ↑ Changes Perceiving Time/Space^a; ↑ HR (immediately); ↑ calmness; = Neurocognition (overall)
Wilsey et al., 2016 [60]				6.7% delta 9-THC vaporized cannabis (4-8 puffs) f/u: 60, 120, 180, 240, 300, 360, 420min		Placebo	↑ Confused^a; ↑ Desires More^a; ↑ Hungry^a; ↑ Difficulty Paying Attention/ Remembering Things^a; ↑ “Good Drug* Effect”^a; ↑ “Bad Drug Effect”^a; ↑ High^a; ↑ Drunk^a; ↑ Impaired^a; ↑ Stoned^a; ↑ Sedated^a; ↑ Nausea^a; ↑ Changes Perceiving Space/Time^a
Pre-/Post-Studies (SCI samples)
Kogel et al., 1995 [76]	SCI staff selected. Chronic problematic spasticity that has not responded to more commonly prescribed spasmolytic medications.		NR	Dronabinol (15.0 mg - 60.0mg/d) f/u: 5d		Baseline	↓ Subjective Concentration; ↓ vigor; = objective concentration; ↑ >1 dysphoric mood scale

Abbreviations: ↑: increase; ↓: decrease; =: no change; ^adata listed not limited to people with SCI; AS: Ashworth Scale; BP: blood pressure; CBD: cannabidiol; CT-3: 1’,1’-dimethylheptyl-Δ8-tetrahydrocannabinol-11-oic acid in capsules; d: day; ECG: electrocardiogram; f/u: follow-up; HR: heart rate; MAS: Modified Ashworth Scale; MC: Medical Cannabis; MCC: maximal cystometric capacity; mo: month; N/A: not applicable; NR: not reported; RR: respiratory rate; SOMC: short orientation-memory-cognition test; temp: temperature; THC: tetrahydrocannabinol; UC: University California; VAS: visual analog scale; wt: weight; y: year. *denotes that higher dose was significant vs lower dose; ^adenotes p<0.0001; ^bdenotes p<0.001; ^cdenotes p=0.001; ^ddenotes p=0.003; ^edenotes p<0.01; ^fdenotes p=0.02; ^gdenotes p=0.028; ^hdenotes p=0.03; ⁱdenotes p<0.03; ^jdenotes p<0.05; ^kdenotes p=0.075.