Table 4.

Cannabinoids in clinical TBI populations

Cannabis use	Dose	Study type	n	Injury	Time frame	Results	References
Phytocannabinoids
Self-reported voluntary use of cannabis	n/a	Prospective Observational	307	mTBI; physician diagnosed	Recruitment within 1 week of injury and follow-up at least 4 week post-injury	Cannabis use was not associated with improved recovery rate; cannabis use was associated with reduced symptom severity 3–4 week post-injury	[144]
Self-reported voluntary use of cannabis	n/a	Survey	163	mTBI; United States Military Veterans	Variable (reported use in past month)	Cannabis was used for management of mTBI-related symptoms (sleep, pain, neuropsychiatric symptoms); cannabis use alone was not sufficient for symptom relief	[148]
THC-positive toxicology screen	n/a	Retrospective observational	538	TBI, variable severity	Toxicology screen upon presentation to hospital	Positive THC screen was associated with lower mortality than patients with negative THC screen	[145]
THC-positive toxicology screen	n/a	Retrospective observational	4849	Trauma (severe) with TBI	Toxicology screen upon presentation to hospital	Positive THC screen was associated with shorter hospital stay and shorter duration of ventilator use	[146]
THC-positive toxicology screen	n/a	Retrospective observational	2754	Severe TBI	Toxicology screen upon presentation to hospital	Positive THC screen was associated with lower risk of hemorrhagic stroke; no effect on thromboembolic outcomes, mortality, or length of hospital stay	[147]
Synthetic cannabinoids
Dexanabinol (synthetic cannabinoid derivative; NMDA receptor antagonist)	48 mg or 150 mg (i.v.; single administration)	Phase II RCT (not powered to test efficacy)	67	Severe, closed-head TBI (score of 4–8 on Glasgow Coma Scale)	Within 6 h of injury	Primary Outcome: Treatment was safe and well-tolerated Additional Outcomes: Treatment lowered intracranial pressure; reduced hypotensive episodes; improved cranial perfusion pressure; associated with improved recovery 1 month post-injury	[149]
Dexanabinol (synthetic cannabinoid derivative; NMDA receptor antagonist)	150 mg (i.v.; single administration)	Phase III RCT	861	TBI (score of 2–5 on Glasgow Coma Scale)	Within 6 h of injury	Primary Outcome: Treatment was safe and well-tolerated. No evidence of improved recovery with treatment 6 month post-injury	[150]