One of the principal mechanisms associated with the maintenance of and relapse to substance use is stress. Preclinical models demonstrate that acute and chronic exposure to stress increases the initiation, escalation, and reinstatement of drug-seeking and self-administration behavior.12,13 This has been found in animal models using neonatal stress, social defeat stress, social isolation, footshock, pharmacologic stress, restraint stress, and novelty stress, as well as in animals with varying genetic backgrounds (e.g., the alcohol-preferring (P) rat).12 In humans, laboratory studies demonstrate that stress increases drug craving, decreases the ability to resist drug use, and increases self-administration behavior.12,14,15 In alcohol-dependent individuals, stress exposure has been found to induce an enhanced and persistent alcohol craving state and increased anxiety and negative emotions.16,17 Likewise, smokers (35%–100%) often cite stress as a major factor contributing to relapse episodes,18,19 and individuals report heightened tobacco craving, smoke more intensely, and report greater satisfaction and reward from smoking following stress exposure in the human laboratory.14 Similar human laboratory studies have examined the effects of stress on cannabis and opioid craving and self-administration behavior, finding that cannabis is often
