Acute and Short-term Effects of CBD on Cue-induced Craving in Drug-abstinent Heroin-dependent Humans

There has been an epidemic rise in heroin abuse and overdose in recent years. Of the more
than one million people suffering today from opiate dependency, less than a quarter of such
individuals receive treatment. Pharmacotherapeutic approaches traditionally have targeted mu
opioid receptors since heroin and its metabolites bind with highest affinity to this receptor
subtype. Although such treatment strategies have improved substance abuse outcomes, they do
not effectively block opiate craving and thus are still associated with high rates of
relapse. Using a strategy of indirectly regulating neural systems to modulate opioid-related
behavior, our preclinical rodent studies consistently demonstrated that cannabidiol (CBD), a
nonpsychoactive component of cannabis, specifically inhibited cue-induced heroin-seeking
behavior. CBD's selective effect on drug-seeking behavior was pronounced after 24 hrs and
endured even two weeks after the last drug administration following short-term CBD exposure.
The fact that drug craving is generally triggered by exposure to conditioned cues suggests
that CBD might be an effective treatment for heroin craving, specially given its protracted
impact on behavior. CBD has already been shown in Phase I of our study and in various
clinical studies to be well tolerated with a wide safety margin in human subjects. CBD thus
represents a strong candidate for the development as a potential therapeutic agent in humans
for opioid craving and relapse prevention. Preliminary pilot study showed CBD decreased
craving. It is the goal of the current study to more fully characterize the effects of CBD
administration on cue-induced craving in drug-abstinent heroin-dependent subjects using a
random double blind design during a post-acute (greater than 6 days since last use) heroin
withdrawal period. Study participants will be administered CBD during 3 test sessions and
studied for the effects on cue-induced craving during those sessions as well as one week
after the final CBD administration on the final test day (session 4).

Inclusion Criteria:

- Must be between 21 and 65 years old

- Must have an opiate dependence that meets criteria set in the Structured Clinical
Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Structured
Clinical Interview for DSM (SCID-V) over the last three months

- No opioid use in the past 7 days (will be verified via urine drug screen and opiate
metabolite test)

Exclusion Criteria:

- Using any psychoactive drug (other than nicotine) any time up to test session 3

- Having a diagnosis of drug dependence (except for heroin or nicotine) in the past 3
months, based on the SCID-V interview criteria

- Being maintained on methadone or buprenorphine, or taking opioid antagonists such as
naltrexone

- Having a positive a drug screen

- Showing signs of acute heroin withdrawal symptoms

- Having medical conditions, including Axis I psychiatric conditions under DSM-V
(examined using the Mini International Neuropsychiatric Interview [MINI])

- Having a a history of cardiac disease, arrhythmias, head trauma, and seizures

- Having a history of hypersensitivity to cannabinoids

- Arriving to the study site visibly intoxicated as determined by a clinical evaluation
for signs and symptoms of intoxication and as verified by a drug screen

- Participating in a another pharmacotherapeutic trial in the past 3 months

- Being pregnant of breastfeeding

- Not using or irregularly using appropriate methods of contraception such as hormonal
contraceptives (e.g., Depo-Provera, Nuva-Ring), an intrauterine device (IUD), or
double barrier method (combination of any two barrier methods used simultaneously,
e.g., condoms, spermicide, diaphragms)