Cannabidiol in Humans—The Quest for Therapeutic Targets
Abstract
:1. Introduction
2. Pharmacokinetics
3. Pharmacodynamics
4. Methods
5. Results
5.1. Experimental Studies in Healthy Controls
5.1.1. Oral or Intravenous CBD-Alone
5.1.2. Oral CBD/Ketamine
5.1.3. Oral CBD/Nabilone
Study | N (CBD) | Dosing | Outcome (≥ greater; ≤ less) |
---|---|---|---|
Hollister [38] | 9 (5) | Fixed-dose; CBD 100 mg, PO; CBD 30 mg, IV | CBD = no subjective or physiological effects |
Consroe et al. [39] | 10 (10) | Fixed-dose; CBD 200 mg, PO | CBD = PBO (time production)
CBD = PBO (finger tapping) CBD = PBO (cancellation test) CBD = PBO (differential aptitude test) |
Zuardi et al. [40] | 11 (11) | Fixed-dose; CBD 300 mg or 600 mg, PO | CBD > PBO (sedation)
CBD < PBO (normal circadian decrease in cortisol level) |
Zuardi et al. [41] | 40 (10) | Fixed-dose; CBD 300 mg; DZP 10 mg; IPS 5 mg, PO | DZP < IPS < CBD < PBO (speech test-induced anxiety) |
Crippa et al. [42] | 10 (10) | Fixed-dose; CBD 400 mg, PO | CBD > PBO (mental sedation)
CBD < PBO (anxiety) |
Borgwardt
et al. [43] Winton-Brown et al. [44] Fusar-Poli et al. [45,46] | 15 (15) | Fixed-dose; CBD 600 mg; ∆9-THC 10 mg, PO | CBD < PBO < ∆9-THC (skin conductance response to fearful faces)
CBD < PBO (anxiety p = 0.06) CBD = PBO (sedation, intoxication) |
Hallak et al. [47] | 10 (10) | Fixed dose; CBD 600 mg, PO; ketamine 0.25 mg/kg, IV | CBD > PBO (ketamine-induced activation [BPRS])
CBD = PBO (ketamine-induced positive and negative symptoms) |
Leweke et al. [48] | 9 (9) | Fixed-dose; CBD 200 mg; NAB 1 mg, PO | NAB > CBD + NAB > CBD (binocular depth perception deficit)
CBD & NAB > PBO (sedation) NAB > CBD + NAB > CBD & PBO (intoxication) |
Karniol et al. [49] | 40 (5) | Fixed-dose; CBD 15 mg, 30 mg, 60 mg; ∆9-THC
30 mg, PO | CBD [15 mg] + ∆9-THC > ∆9-THC (pulse rate)
CBD [30 & 60 mg] + ∆9-THC < ∆9-THC (pulse rate) ∆9-THC > CBD [all doses] + ∆9-THC (time production impairment) |
Hollister and Gillespie [50] | 15 (15) | Fixed-dose; CBD 40 mg; ∆9-THC 20 mg, PO | CBD + ∆9-THC > ∆9-THC (duration and intensity of intoxication)
CBD + ∆9-THC > ∆9-THC (time to onset of intoxication) CBD + ∆9-THC = ∆9-THC (pulse rate) |
Zuardi et al. [51] | 8 (8) | Fixed-dose; CBD 1 mg/kg; ∆9-THC 0.5 mg/kg, PO | ∆9-THC > CBD + ∆9-THC (anxiety, intoxication)
CBD + ∆9-THC = ∆9-THC (pulse rate) |
Juckel
et al. [52] Roser et al. [53,54] | 24 (24) | Fixed-dose; CBD 5.4 mg; ∆9-THC 10 mg, PO | CBD + ∆9-THC > ∆9-THC (MMN amplitude)
CBD + ∆9-THC < PBO (right-hand tapping frequency) CBD + ∆9-THC = ∆9-THC (P300 amplitude) |
Nicholson et al. [55] | 8 (8) | Fixed-dose; CBD 15 mg; ∆9-THC 15 mg, OMC | CBD + ∆9-THC < ∆9-THC (impairment of immediate and delayed word recall)
CBD + ∆9-THC = ∆9- THC (digit symbol substitution, choice reaction time, sustained attention, six-letter memory recall) CBD + ∆9-THC > ∆9-THC (awake time before sleep, sleepiness and fatigue upon awakening) |
Dalton et al. [56] | 15 (15) | Fixed-dose; CBD 150 µg/kg; ∆9-THC 25 µg/kg, INH | ∆9-THC > CBD + ∆9-THC (intoxication)
CBD + ∆9-THC & ∆9-THC > CBD (disturbance of stability of stance, motor performance, mental performance, manual coordination) |
Ilan et al. [57] | 23 (23) | Fixed-dose; CBD (1% versus 0.2%) ∆9-THC (3.6% versus 1.8%), INH | CBD + ∆9-THC = ∆9-THC (heart rate, intoxication)
CBD [low] + ∆9-THC [high] > CBD [high] + ∆9-THC [high] (anxiety) CBD [high] + ∆9-THC [low] > CBD [low] + ∆9-THC [low] (anxiety) |
Bhattacharyya et al. [58] | 6 (6) | Fixed-dose; CBD 5 mg; ∆9-THC 1.25 mg, IV | ∆9-THC > CBD + ∆9-THC (positive symptoms) |
Study | N (CBD) | Subjects | Time | Dosing | Outcome(s) (≥ greater; ≤ less) |
---|---|---|---|---|---|
Consroe et al. [15] | 15 (15) | Huntington’s | 6 weeks | Flexible-dose; CBD 700 mg #, PO | CBD = PBO (chorea severity) |
Carlini and Cunha [ 59] | 15 (15) | Insomnia | Acute | Fixed-dose; CBD 40 mg, 80 mg, 160 mg, NTZ 5 mg PO | CBD [160 mg] > PBO (sleep duration)
CBD [all doses] < PBO (dream recall) CBD [all doses] = NTZ = PBO (sleep induction) |
Cunha et al. [61] | 15 (8) | Epilepsy | 2–18 weeks | Flexible-dose; CBD 200–300 mg, PO | CBD < PBO (seizures) |
Crippa et al. [62] | 10 (10) | Social anxiety disorder | Acute | Fixed-dose; CBD 400 mg, PO | CBD < PBO (anxiety) |
Bergamaschi et al. [63] | 24 (12) | Social anxiety disorder | Acute | Fixed-dose; CBD 600 mg, PO | CBD < PBO (anxiety) |
Leweke et al. [64] | 42 (21) | Schizophrenia | 4 weeks | Fixed-dose; CBD 600 mg; AMI 600 mg, PO | CBD = AMI (positive symptoms) |
Zuardi et al. [65] | 3 (3) | Schizophrenia | 4 weeks | Fixed-dose; CBD—up to 1,280 mg, PO | CBD = PBO (positive and negative symptoms) |
Zuardi et al. [66] | 2 (2) | Bipolar I disorder | 4 weeks | Fixed-dose; CBD—up to 1,280 mg, PO | CBD = PBO (mania) |
Hallak et al. [67] | 28 (9) | Schizophrenia | Acute | Fixed-dose; CBD 300 mg or 600 mg, PO | CBD [600 mg] > CBD [300 mg] & PBO (Stroop Color Word Test errors) |
Killestein et al. [68,69] | 16 (16) | Multiple sclerosis | 4 weeks | Flexible-dose; ∆9-THC 5–10 mg; Cannabis extract 5–10 mg (20–30% CBD), PO | CBD + ∆9-THC > ∆9-THC > PBO (side-effects)
CBD + ∆9-THC & ∆9-THC = PBO (spasticity) CBD + ∆9-THC > PBO (TNF-alpha) |
Zajicek
et al. [70] (CAMS) | 630 (211) | Multiple sclerosis | 15 weeks | Flexible-dose; CBD (to 12.5 mg/d); ∆9-THC (to 25 mg/d), PO | CBD + ∆9-THC & ∆9-THC = PBO (pain)
CBD + ∆9-THC & ∆9-THC = PBO (spasticity) CBD + ∆9-THC & ∆9-THC = PBO (spasms) CBD + ∆9-THC & ∆9-THC = PBO (sleep quality) |
Freeman
et al. [71] (CAMS-LUTS) | 255 (88) | Multiple sclerosis | 13 weeks | Flexible-dose; CBD (to 12.5 mg/d); ∆9-THC (to 25 mg/d), PO | CBD + ∆9-THC & ∆9-THC < PBO (urinary incontinence) |
Strasser et al. [72] | 243 (95) | Cancer anorexia | 6 weeks | Fixed-dose; CBD 2 mg; ∆9-THC 5 mg, PO | CBD + ∆9-THC & ∆9-THC = PBO (appetite, nausea, mood) |
Johnson et al. [73] | 177 (60) | Cancer pain | 2 weeks | Flexible-dose; CBD 20–30 mg; ∆9-THC 22–32 mg, OMC | CBD + ∆9-THC < PBO (pain; NRS)
∆9-THC < PBO (pain; BPI-SF) CBD + ∆9-THC > PBO (nausea) CBD + ∆9-THC & ∆9-THC > PBO (cognitive deficits) |
Brady et al. [74] | 15 (15) | Multiple sclerosis | 8 weeks | Flexible-dose; CBD & ∆9-THC 34 mg #, OMC | ∆9-THC < BAS (spasticity)
∆9-THC > BAS (sleep quality) CBD + ∆9-THC & ∆9-THC < BAS (pain) CBD + ∆9-THC & ∆9-THC < BAS (incontinence) |
Wade et al. [75] | 20 (20) | Multiple sclerosis (14/20) + neuropathic pain | 2 weeks | Flexible-dose; CBD & ∆9-THC 45 mg #, OMC | ∆9-THC & CBD < PBO (pain; VAS)
CBD + ∆9-THC & ∆9-THC & CBD = PBO (pain; NRS) CBD + ∆9-THC & ∆9-THC < PBO (spasms; VAS) ∆9-THC > PBO (appetite; VAS) CBD + ∆9-THC > PBO (sleep quality; VAS) ∆9-THC > PBO (memory impairment) |
Notcutt et al. [76] | 34 (34) | Multiple sclerosis (16/34) + neuropathic pain | 5 weeks | Flexible-dose; CBD & ∆9-THC 2.5 mg per spray, OMC | CBD + ∆9-THC & ∆9-THC < CBD & PBO (pain)
CBD + ∆9-THC & ∆9-THC > CBD > PBO (sleep quality) |
Berman et al. [77] | 48 (48) | Neuropathic pain | 2 weeks | Flexible-dose; CBD & ∆9-THC 20 mg or 8–10 sprays per day #, OMC | CBD + ∆9-THC & ∆9-THC < PBO (pain; BS-11)
∆9-THC < PBO (pain; SF-MPQ) CBD + ∆9-THC & ∆9-THC = PBO (pain disability) CBD + ∆9-THC & ∆9-THC > PBO (sleep quality) |
5.1.4. Oral CBD/∆9-THC
5.1.5. Oromucosal CBD/∆9-THC
5.1.6. Smoked or Intravenous CBD/∆9-THC
5.2. Clinical Trials in Patient Populations
5.2.1. Oral CBD-Alone
5.2.2. Oral CBD/∆9-THC
5.2.3. Oromucosal CBD/∆9-THC
6. Discussion
7. Conclusions
Acknowledgements
References
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Zhornitsky, S.; Potvin, S. Cannabidiol in Humans—The Quest for Therapeutic Targets. Pharmaceuticals 2012, 5, 529-552. https://doi.org/10.3390/ph5050529
Zhornitsky S, Potvin S. Cannabidiol in Humans—The Quest for Therapeutic Targets. Pharmaceuticals. 2012; 5(5):529-552. https://doi.org/10.3390/ph5050529
Chicago/Turabian StyleZhornitsky, Simon, and Stéphane Potvin. 2012. "Cannabidiol in Humans—The Quest for Therapeutic Targets" Pharmaceuticals 5, no. 5: 529-552. https://doi.org/10.3390/ph5050529
APA StyleZhornitsky, S., & Potvin, S. (2012). Cannabidiol in Humans—The Quest for Therapeutic Targets. Pharmaceuticals, 5(5), 529-552. https://doi.org/10.3390/ph5050529