Table 2.
CBD effects on learned fear processing in male animals
| Reference | Test used | Strain, species, effective dose and route/site of administration | Effect | Pharmacological mechanism |
|---|---|---|---|---|
| Studies conducted in operant conditioning paradigms | ||||
| Silveira Filho and Tufik, 1981 | Geller‐Seifter conflict test | Wistar rats, 100 mg·kg−1, i.p. | No effect | Not tested |
| Musty et al. (1985) | Vogel punished licking test | Sprague–Dawley rats, 5–10 mg·kg−1, i.p. | Anxiolytic (bell‐shaped dose–response curve) | Not tested |
| Moreira et al. (2006) | Vogel punished licking test | Wistar rats, 10 mg·kg−1, i.p. | Anxiolytic | Not blocked by BZD antagonism (flumazenil) |
| Gomes et al. (2011) | Vogel punished licking test | Wistar rats, 30–60 nmol, intra‐BNST | Anxiolytic | 5‐HT1A receptor activation |
| Studies conducted in classical (Pavlovian) conditioning paradigms | ||||
| Zuardi and Karniol, 1983 | AFC | Wistar rats, 10 mg·kg−1, i.p. | Anxiolytic (decreased fear expression) | Not tested |
| Resstel et al. (2006) | CFC | Wistar rats, 10 mg·kg−1, i.p. | Anxiolytic (decreased fear expression) | Not tested |
| Bitencourt et al. (2008) | CFC | Wistar rats, 6.4 nmol, i.c.v. | Facilitated fear memory extinction | Indirect CB1 receptor activation |
| Lemos et al. (2010) | CFC | Wistar rats, 10 mg·kg−1, i.p. | Anxiolytic (decreased fear expression) | Not tested |
| Lemos et al. (2010) | CFC | Wistar rats, 30 nmol, intra‐PL cortex | Anxiolytic (decreased fear expression) | Not tested |
| Lemos et al. (2010) | CFC | Wistar rats, 30 nmol, intra‐IL cortex | Anxiogenic (increased fear expression) | Not tested |
| ElBatsh et al. (2012) | CFC | Lister‐hooded rats, 10 mg·kg−1, i.p. daily for 14 days | Anxiogenic (increased fear expression) | Decreased hippocampal BDNF and TrkB, reduced frontal cortex phospho‐ERK1/2 expression |
| Gomes et al. (2012) | CFC | Wistar rats, 30–60 nmol, intra‐BNST | Anxiolytic (decreased fear expression) | 5‐HT1A receptor activation |
| Levin et al. (2012) | CFC | Wistar and SHR rats, 1–15 mg·kg−1, i.p. | Anxiolytic (decreased fear expression) and/or disrupted fear memory formation (Wistar rats only) | Not tested |
| Stern et al. (2012) | CFC | Wistar rats, 3–30 mg·kg−1, i.p. | Disrupted fear memory reconsolidation (bell‐shaped dose response curve) | Indirect CB1 receptor activation |
| Do Monte et al. (2013) | CFC | Long–Evans hooded rats, 1.3 nmol, intra‐IL cortex | Facilitated fear memory extinction | Indirect CB1 receptor activation |
| Cheng et al. (2014) | AFC | C57BL/6 J mice, 20 mg·kg−1, i.p. daily for 21 days | No effect | Not tested |
| Fogaça et al. (2014) | CFC | Wistar rats, 30 nmol, intra‐PL cortex | Anxiolytic (decreased fear expression) | 5‐HT1A receptor activation |
| Gazarini et al. (2015) | CFC | Wistar rats, 10 mg·kg−1, i.p. | Disrupted fear memory reconsolidation | Not tested |
| Stern et al. (2014) | CFC | Wistar rats, 10 mg·kg−1, i.p. | Disrupted fear memory reconsolidation | Indirect CB1 receptor activation in PL cortex |
| Marinho et al. (2015) | CFC | Wistar rats, 30 nmol, intra‐IL cortex | Anxiogenic (increased fear expression) | 5‐HT1A receptor activation |
| Stern et al. (2015) | CFC | Wistar rats, 1 mg·kg−1 + THC 0.1 mg·kg−1, i.p. | Disrupted fear memory reconsolidation | Not tested |
| Norris et al. (2016) | OFC | Sprague Dawley rats, 0.03–0.32 nmol, intra‐nucleus accumbens shell | Disrupted fear memory formation (acquisition) | 5‐HT1A receptor activation |
| Song et al. (2016) | CFC | Lister hooded rats, 10 mg·kg−1, i.p., before extinction (after weak or strong conditioning) | Impaired or enhanced extinction after weak or strong conditioning, respectively | Not tested |
| Jurkus et al. (2016) | AFC | Lister hooded rats, 5–20 mg·kg−1, i.p. | Anxiolytic (decreased fear expression) at highest dose, no effect on extinction | Not tested |
| Stern et al. (2016) | CFC | Wistar rats, 10–30 mg·kg−1, i.p. | Disrupted fear memory consolidation | Indirect CB1 or CB2 receptor activation |
AFC, auditory fear conditioning; BZD, benzodiazepine; CFC, contextual fear conditioning; OFC, olfactory fear conditioning.