Self-administration of inhaled delta-9-tetrahydrocannabinol and synthetic cannabinoids in non-human primates

Abstract

Cannabis and synthetic cannabinoids are abused in spite of possible adverse health consequences. The current study investigated the reinforcing effects of an ecologically relevant mode of administration (inhalation) of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, and three synthetic cannabinoids detected in synthetic cannabinoid products (JWH-018, JWH-073, and HU-210) in non-human primates (NHPs). Male and female (N = 4 each) rhesus macaques were trained to inhale warm air via a metal stem to receive a candy reinforcer, an alcohol aerosol vehicle was then paired with the candy. Dose-dependent responding for inhaled aerosols of THC (2.0-16.0 μg/kg/inhalation), JWH-018 (0.2-1.6 μg/kg/inhalation), JWH-073 (2.0-8.0 μg/kg/inhalation), and HU-210 (1.0-8.0 μg/kg/inhalation) was established using a fixed-ratio five schedule of reinforcement and compared to vehicle (alcohol) self-administration. Dose-dependent responding for inhaled heroin (25.0-100.0 μg/kg/inhalation), a known reinforcer in NHPs, was also established. Responding approximated vehicle levels for many drug doses tested, but at least half of the monkeys responded for ≥ one dose of each cannabinoid and heroin above vehicle, with the exception of THC. Drug deliveries calculated as percent vehicle followed a prototypical inverted-U shaped dose-response curve for cannabinoids and heroin except for THC and JWH-018 (in males). Grouped data according to sex demonstrated that peak percent of vehicle reinforcers earned for THC was greater in males than females, whereas peak percent of vehicle reinforcers earned for JWH-018, HU-210, and heroin were greater in females than males. These findings indicate minimal reinforcing effects of CB1 receptor agonists when self-administered by NHPs via aerosol inhalation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Figure 1.

Average (± SEM) aerosol deliveries earned as a function of THC dose for individual female (1A, •) and male (1B, ■) monkeys. Aerosol deliveries earned averaged according to sex (± SEM) depicted in the right panels. Average (± SEM) vehicle aerosol deliveries are indicated by open symbols (○ for females, □ for males) and gray bar.

Figure 2.

Average (± SEM) aerosol deliveries earned as a function of JWH-018 dose for individual female (2A, •) and male (2B, ■) monkeys. Aerosol deliveries earned averaged according to sex (± SEM) depicted in the right panels. Average (± SEM) vehicle aerosol deliveries are indicated by open symbols (○ for females, □ for males) and gray bar.

Figure 3.

Average (± SEM) aerosol deliveries earned as a function of JWH-073 dose for individual female (3A, •) and male (3B, ■) monkeys. Aerosol deliveries earned averaged according to sex (± SEM) depicted in the right panels. Average (± SEM) vehicle aerosol deliveries are indicated by open symbols (○ for females, □ for males) and gray bar.

Figure 4.

Average (± SEM) aerosol deliveries earned as a function of HU-210 dose for individual female (4A, •) and male (4B, ■) monkeys. Aerosol deliveries earned averaged according to sex (± SEM) depicted in the right panels. Average (± SEM) vehicle aerosol deliveries are indicated by open symbols (○ for females, □ for males) and gray bar.

Figure 5.

Average (± SEM) aerosol deliveries earned as a function of heroin dose for individual female (5A, •) and male (5B, ■) monkeys. Aerosol deliveries earned averaged according to sex (± SEM) depicted in the right panels. Average (± SEM) vehicle aerosol deliveries are indicated by open symbols (○ for females, □ for males) and gray bar.

Figure 6.

Average (± SEM) aerosol deliveries delivered for each active drug dose calculated as percent of the vehicle for each drug. Data depicted as a function of drug (THC, JWH-018, JWH-073, HU-210, and heroin) and sex (females in 6A, • and males in 6B, ■).