Table 5.
Human clinical studies and trials on cannabinoids
| Disease | eCB/CB | Trial | Outcome | Reference |
|---|---|---|---|---|
| Stroke | Rimonabant (SR141716) | Comprehensive Rimonabant Evaluation Study of Cardiovascular ENDpoints Outcomes (CRESCENDO) trial | Trial discontinued due to side effects | Topol et al., 2010 |
| Epilepsy | CBD | Prospective study | Reduced interictal epileptiform discharge frequency; improved sleep | Klotz et al., 2021 |
| Nonrandomized controlled trial in children aged 3 to 18 years | CBD transdermal gel reduced frequency of tonic-clonic seizures; improved social engagement, sleep, and cognitive function | Scheffer et al., 2021 | ||
| Open-label extension trial | CBD transdermal patch led to 60.8% of the participants exhibiting ≥ 50% decrease in seizures | O’Brien et al., 2022 | ||
| Genetic study - gene variants | Genetic associations between gene variants, CBD tolerability, seizure reduction were determined | Davis et al., 2021 | ||
| Tuberous sclerosis complex seizures | CBD | Double-blind, placebo-controlled trial | Reduction in primarily focal seizures/month; 50% of patients had 50% reduction in seizures | Thiele et al., 2021, 2022 |
| CBD | Randomized, placebo-controlled, phase 3 trial | CBD-mediated decline in seizures emerged on day 6 and by day 10 | Wu et al., 2022 | |
| Lennox-Gastaut syndrome seizures | CBD | GWPCARE5 open label extension trial | CBD led to 48–71% median decrease in atonic seizures and 48–68% decrease in all seizures | Patel et al., 2021 |
| Multiple sclerosis | THC/CBD oro-mucosal spray | 20 MS patients (10 with and 10 without neuropathic pain) with clinical and neurophysiological assessment | Nabiximols reduced pain rating and improved quality of life | Russo et al., 2016 |
| Pilot, single center, open, and prospective study | Positive subjective effect on MS-related spasticity | Contin et al., 2018 | ||
| SAVANT RCT study (post hoc analysis) | Reduced the average spasticity and pain severity scores in all subgroups | Meuth et al., 2020 | ||
| Alzheimer’s disease | THC, synthetic cannabinoids | Meta-analysis of clinical studies | Trend toward improvement in agitation with synthetic cannabinoids | Ruthirakuhan et al., 2019 |
| Parkinson’s disease | THC, CBD | 119 patients evaluated in outpatient clinic | THC had no effect; possible CBD effect in improving quality of life in PD patients | Chagas et al., 2014 |
| Huntington’s disease | Cannabinoids | 7 early-onset HD patients | Reduction in dystonia and motor symptoms; led to improvement in fine motor skills and gait | Saft et al., 2018 |
| CBD | Double-blind, randomized cross-over design; 15 neuroleptic-free patients with HD | No effect on chorea severity | Consroe et al., 1991 | |
| Pain | Inhaled cannabis vapor (Bedrocan, Bediol, Bedrolite & placebo) | Randomized, placebo-controlled, crossover trial | Bediol reduced spontaneous pain scores | van de Donk et al., 2019 |
| Inhaled cannabis vapor (THC/CBD) | Randomized crossover trial with individuals with sickle cell disease | No reduction in pain or in pain interference ratings, but improvement in mood | Abrams et al., 2020 | |
| THC (oral) | Randomized placebo-controlled crossover study with evoked pain tasks | THC reduced pain from electrical and pressure stimuli and altered calmness and alertness | van Amerongen et al., 2018 | |
| Oral THC-rich cannabis oil | Double-blind, randomized, placebo-controlled trial with women with fibromyalgia pain | Decrease in the Fibromyalgia Impact Score (reduced pain) | Chaves et al., 2020 | |
| Inhaled THC (metered dose) | Randomized, double-blinded, placebo-controlled, cross-over trial with 27 patients with chronic pain | Decrease in pain intensity | Almog et al., 2020 | |
| Aerosolized THC | Pain from diabetic peripheral neuropathy | THC reduced pain ratings at moderate levels | Wallace et al., 2020 | |
| Sublingual THC administration | Measurement of functional brain changes and THC improvement of chronic neuropathic pain | Decreased in pain associated with anterior cingulate cortex-sensorimotor cortex and dorsolateral prefrontal cortex function | Weizman et al., 2018 | |
| Intravenous THC | Exploratory randomized, double-blind, placebo-controlled, cross-over study using evoked pain in healthy participants | No analgesic effects in hyperalgesia or induced thermal, electrical, chemical, or mechanical pain | Schindler et al., 2020 | |
| Oral CBD | Double-blind, placebo-controlled, clinical study in healthy subjects | No effect on pain threshold/ tolerance in cold pressor test; increased pain ratings | Arout et al., 2022 | |
| oral CBD | Random, double-blinded, placebo-controlled trial on pain associated with surgical procedures | Pain score reduced on first day after procedure; improved patient satisfaction with pain control | Alaia et al., 2022 | |
| Topical CBD (with shea butter) | Therapeutic activity of CBD for thumb basal joint arthritis pain | Improvement in patient-reported visual analogue scale pain rating | Heineman et al., 2022 | |
| Synthetic CBD (add-on therapy) | Randomized, double-blind, placebo-controlled trial for for osteoarthritis or psoriatic arthritis pain | Exhibited no therapeutic effects; did not improve depression, anxiety, or sleep quality | Vela et al., 2022 | |
| Topically CBD oil | Randomized, placebo-controlled, crossover trial for neuropathic pain | Decreased intense and sharp pain, cold and itch | Xu et al., 2020 | |
| Neuropsychiatric disorders | CBD | Double-blind, placebo-controlled Pavlovian fear-conditioning study | Improved consolidation of extinction learning | Das et al., 2013 |
| THC and CBD | Regional brain activation, electrodermal activity, and anxiety ratings to determine effects of THC & CBD on anxiety | THC exacerbated anxiety; CBD decreased anxiety | Fusar-Poli et al., 2009 | |
| Transdermal CBD gel (ZYN002) | Measure effectiveness of transdermal CBD gel, ZYN002, in children with FXS | Decreased the anxiety, depression, and mood scores | Heussler et al., 2019 | |
| CBD | Add-on CBD treatment administered in participants on antidepressant medication | Reduced in anxiety and depression scores after several weeks | Berger et al., 2022 | |
| CBD | Administered to patients with psychosis followed by functional magnetic resonance imaging during a verbal learning exercise | Led to a trend toward a decrease in psychotic symptoms | O’Neill et al., 2021 | |
| AEA | Cerebrospinal fluid (CSF) measured from schizophrenic patients | AEA concentrations in CSF negatively correlated with psychotic symptoms | Leweke et al., 2007 |
AEA: N-arachidonoylethanolamine; CB: cannabinoid; CBD: cannabidiol; eCB: endocannabinoid; FXS: Fragile X syndrome; HD: Huntington’s diseases; MS: multiple sclerosis; THC: Δ9-Tetrahydro-cannabinol.