The effects of cannabidiol (CBD) on Δ⁹-tetrahydrocannabinol (THC) self-administration in male and female Long-Evans rats.

Abstract

Despite widespread cannabis use in humans, few rodent models exist demonstrating significant Δ⁹-tetrahydrocannabinol (THC) self-administration, possibly due to THC's co-occurring aversive effects, which impact drug reinforcement. Cannabis contains a number of phytocannabinoids in addition to THC, one of which, cannabidiol (CBD), has been reported to antagonize some of the aversive effects of THC. Given such effects of CBD, it is possible that it might influence THC intravenous self-administration in rodents. Accordingly, male and female Long-Evans rats were trained to self-administer THC over a 3-week period and then were assessed for the effects of CBD on responding for THC at 1:1 and 1:10 dose ratios or for the establishment of cocaine self-administration (as a positive control for drug self-administration). Consistent with previous research, THC self-administration was modest and only evident in a subset of animals (and unaffected by sex). Cocaine self-administration was high and evident in the majority of animals tested, indicating that the design was sensitive to drug reinforcement. There was no effect of CBD pretreatment on THC intravenous self-administration at any CBD:THC dose ratio. Future developments of animal models of THC self-administration and the examination of factors that affect its display remain important to establish procedures designed to assess the basis for and treatment of cannabis use and abuse. (PsycINFO Database Record

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

“…The cannabis extracts used in the current study contain THC, CBD, and other naturally-occurring phytocannabinoids, and these Cannabis vapor self-administration phytocannabinoids may mitigate the aversive effects of THC [42]. Notably, CBD facilitates intravenous THC self-administration in rodents [12] (but see [43]) and offsets some of the pharmacological and behavioral effects of THC in humans [44] and rodents [9]. Furthermore, a passive THC+CBD vapor preexposure regimen facilitates the acquisition of intravenous THC+CBD self-administration, possibly by offsetting the novelty of THC intoxication or aversive stimulus properties prior to operant training [12].…”

One Is Not Enough: Understanding and Modeling Polysubstance Use

“…Cannabis contains two principal cannabinoids with varying affinity for cannabinoid (CB) receptors: THC is a partial agonist with moderate affinity for both CB 1 and CB 2 receptors whereas CBD has extremely low affinity for CB 1 and CB 2 receptors and signals through an unknown mechanism (Pertwee, 2008). Interestingly, pretreatment with a range of CBD doses has no effect on THC self-administration (Wakeford et al, 2017), indicating non-overlapping signaling pathways for each cannabinoid. CB 1 receptors are expressed on presynaptic terminals throughout the CNS and are responsible for the psychoactive effects of cannabis, while CB 2 receptors are primarily expressed on immune cells of the CNS and PNS and are primarily responsible for the antinociceptive and anti-inflammatory effects of cannabis (Pertwee, 2008).…”

Self-administration of edible Δ9-tetrahydrocannabinol and associated behavioral effects in mice

“…Therefore, animal models of cannabis administration are extremely valuable for the well-controlled investigation of behavioral and physiological causes and consequences of cannabis use. However, self-administration of cannabinoids in animals has been notoriously difficult to establish (Justinova et al, 2005;Melis et al, 2017;Panagis et al, 2008;Tanda and Goldberg, 2003;Wakeford et al, 2017). Animal studies successfully demonstrating cannabinoid self-administration typically use intravenous delivery (Justinova et al, 2003;Melis et al, 2017;Spencer et al, 2018;Wakeford et al, 2017), a route not used by humans and one requiring invasive surgery.…”

“…However, self-administration of cannabinoids in animals has been notoriously difficult to establish (Justinova et al, 2005;Melis et al, 2017;Panagis et al, 2008;Tanda and Goldberg, 2003;Wakeford et al, 2017). Animal studies successfully demonstrating cannabinoid self-administration typically use intravenous delivery (Justinova et al, 2003;Melis et al, 2017;Spencer et al, 2018;Wakeford et al, 2017), a route not used by humans and one requiring invasive surgery. Moreover, successful intravenous self-administration often involves food deprivation, restraint, and/or prior exposure to experimenteradministered cannabinoids (Fattore et al, 2001;Justinova et al, 2003;Martellotta et al, 1998;Melis et al, 2017;Spencer et al, 2018;Wakeford et al, 2017).…”