Repeated Cannabis Administration on Experimental Pain and Abuse Liability

New York State Psychiatric Institute

Status and phase: Completed; Phase 2

Conditions: Hyperalgesia; Cannabis; Tolerance; Pain

Treatments: Drug: Active Cannabis; Drug: Placebo Cannabis

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04576507

8016

Details and patient eligibility

About

Chronic pain is a significant public health concern in the U.S., for which prescription opioids have historically been the standard treatment. This has resulted in striking rates of opioid use disorders and fatal overdoses. Identifying non-opioid medications for the management of chronic pain with minimal abuse liability is a public health necessity, and cannabinoids are a promising drug class for this purpose. More than 80% of medicinal cannabis users report pain as their primary medical indication. These patients tend to seek products that are low in delta-9-tetrahydrocannabinol (THC; the primary psychoactive, and thus intoxicating, component of cannabis), and high in cannabidiol (CBD), a cannabinoid that purportedly has therapeutic benefit for pain but does not produce intoxicating effects. However, there are few well-controlled human laboratory studies assessing the efficacy of high-CBD cannabis for pain in the context of abuse, and even less is known regarding the effects of daily repeated use of cannabis on pain and its relationship to abuse liability.

The proposed randomized, within-subjects, placebo-controlled 16-day crossover inpatient human laboratory pilot study (N = 16 healthy cannabis users; 8 men, 8 women) will address important gaps in our understanding of the potential therapeutic utility of cannabis for pain: 1) If repeated cannabis use can result in hyperalgesia; 2) If tolerance to the analgesic and abuse-related effects of cannabis develops and is reversible. Two distinct modalities of experimental pain will be assessed: The Cold Pressor Test (CPT) and Quantitative Sensory Testing Thermal Temporal Summation (QST-TTS), and participants will smoke cannabis 3x/day. Throughout the study, experimental pain and abuse-related effects will be assessed, as will sleep and subjective mood assessments.

This protocol is currently suspended due to the NYSPI human subjects research pause and results cannot currently be analyzed and posted. Upon un-suspension, we will analyze the data and post results immediately.

Enrollment: 10 patients

Sex: All

Ages: 21 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Males/non-pregnant females, 21-60 years old
• Current cannabis user
• Able to perform all study procedures

Exclusion criteria

• Use of other illicit drugs
• If medical history, physical and psychiatric examination, or laboratory tests performed during the screening process reveal any significant illness that the study physician deems contraindicated for study participation
• Insensitivity to the cold-water stimulus of the Cold Pressor Test or the heat stimulus of Quantitative Sensory Testing

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

10 participants in 3 patient groups, including a placebo group

Dose A: Standardization Phase

Experimental group

Description:

On the first full inpatient day (Day 1), participants will smoke one specified strength (Dose A; 75% of active cannabis cigarette, 2.98% THC, 4.91% CBD) of cannabis.

Treatment:

Drug: Active Cannabis

Dose B: Placebo Phase

Placebo Comparator group

Description:

Days 2-8 comprises the Placebo phase, in which a second strength (Dose B; 75% of one placebo cannabis cigarette, \<0.01% THC, CBD) of cannabis will be administered 3x/day.

Treatment:

Drug: Placebo Cannabis

Dose A: Active Phase

Experimental group

Description:

Days 9-15 comprise the Active Phase, cannabis Dose A (75% of one active cannabis cigarette, 2.98% THC, 4.91% CBD) will be administered once again, 3x/day.

Treatment:

Drug: Active Cannabis