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Table 2 Phytocannabinoids in TBI models

From: Cannabinoids in traumatic brain injury and related neuropathologies: preclinical and clinical research on endogenous, plant-derived, and synthetic compounds

Treatment

Dose

Route

Frequency

Model

Species

Results

References

THC

1.25 mg/kg

i.p.

Daily ×12, post-injury or 6× intermittent treatments prior to injury

Closed-head lateral impact 3×, 3 days apart (rmTBI)

Sprague–Dawley rats, males and females

Post-rmTBI treatment reduced anxiety behavior in the elevated plus maze and prevented telomere shortening. Effects on depression-like outcomes were sex-dependent

[65]

THC

1 mg/kg

i.p.

1×, 1 h post-injury

Closed-head, weight-drop with rotation (mTBI)

Sprague–Dawley rats, males and females

THC did not affect TBI-induced RotaRod impairment (males); THC impaired RotaRod performance in sham rats (males); THC treatment increased IL-6 after TBI (males); and THC + TBI reduced CB1R density relative to THC alone (females)

[67]

THC

3 mg/kg

i.p.

Daily ×3, post-injury

CCI (with craniotomy)

C57BL/6 J mice, males

Treatment improved RotaRod performance; and upregulated G-CSF, BDNF, GDNF

[68]

THC

3 mg/kg

i.p.

Daily ×3, post-injury

CCI (with craniotomy)

C57BL/6 J mice, males

Treatment reversed CCI-induced impairment in spontaneous alternation Y-maze performance; improved RotaRod performance; and upregulated 2-AG, G-CSF, BDNF, GDNF

[69]

CBD

30 μL, oil 10%

Oral gavage

Daily from days 1–14 and days 50–60 post-injury

Weight-drop mTBI with longitudinal incision

C57BL/6 J mice, males

Treatment reduced pain response; improved sociability; reduced aggression; and restored levels of D-Asp, Glutamate and GABA 14 days after mTBI, but not 60 days after mTBI

[62]

CBD

5, 10, 20 mg/kg

i.p.

30 min before and six h post-injury

Weight-drop TBI with craniotomy (modified Feeney’s model)

Sprague–Dawley rats, males

Treatment (10 mg/kg) downregulated TNF-α, IL-1β, GFAP, AQP4; upregulated claudin-5 and occludin; and reduced edema

[63]

High CBD, low THC preparation

20 mg/mL topical; 20–40 mg/kg

Topical via gel, ± i.p.

Gel applied 1× two min post-injury; i.p. administered 10 min post-injury then daily × 14

CCI (with craniotomy)

Sprague–Dawley and Wistar rats, males and females

Treatment improved vestibulomotor function; improved cognitive function; reduced lesion volume; and attenuated hippocampal injury

[64]