The Pharmacodynamics of Cannabinoid-Caffeine Combinations

NCT05478863 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB00330923
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cannabis and caffeine are two of the most commonly consumed psychoactive substances in the world, with many consumers reporting positive impacts on energy, alertness, and focus. Preliminary evidence has suggested that cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, may mitigate the negative side effects of caffeine (e.g., feeling jittery) without impacting positive or desired effects. CBD also shows potential in reducing undesirable acute effects (e.g., anxiety) of delta-9-tetrahydrocannabinol (THC), the primary intoxicating cannabinoid found in cannabis. Despite these promising findings, little is known about the potential effects of THC, caffeine, and CBD in combination. This double-blind, randomized, placebo-controlled, within-subject crossover study will assess the effects of combinations of THC, CBD, and caffeine (i.e., THC only; THC + caffeine; THC + CBD + caffeine) on subjective energy, arousal, and cognitive performance.

Conditions

Behavioral Pharmacology of Cannabinoids

Outcome Measures

Primary Outcomes (2)

• Change in Driving Performance on the DRiving Under the Influence of Drugs (DRUID®)

  Driving Performance as Measured by the DRiving Under the Influence of Drugs (DRUID®) behavioral task. Higher scores = greater impairment.

  0-, 30-, 90-, 150-, 170-, 240-, 360-, and 480- minutes post drug administration

• Driving Performance on the Driving Simulator

  Driving Performance as Measured by a Driving Simulator task

  170-minutes post drug administration

Secondary Outcomes (5)

• Change in subjective feelings of energy

  0-, 30-, 90-, 150-minutes post drug administration

• Change in subjective feelings of alertness

  0-, 30-, 90-, 150-minutes post drug administration

• Change in subjective feelings of focus

  0-, 30-, 90-, 150-minutes post drug administration

• Change in subjective feelings of jitteriness

  0-, 30-, 90-, 150-minutes post drug administration

• Change in subjective feelings of anxiety

  0-, 30-, 90-, 150-minutes post drug administration

Study Arms (4)

Oral placebo

PLACEBO COMPARATOR

Acute administration of oral placebo three times in study session (Time 0, 60, and 120).

Drug: Oral Placebo

Oral administration of 2.5 mg THC

EXPERIMENTAL

Acute administration of oral THC (2.5 mg) three times in study session (Time 0, 60, and 120).

Drug: Oral THC

Oral administration of 2.5 mg THC + 60 mg caffeine

EXPERIMENTAL

Acute administration of oral THC (2.5 mg) and oral caffeine (60 mg) three times in study session (Time 0, 60, and 120).

Drug: Oral THC; Drug: Oral Caffeine

Oral administration of 2.5 mg THC + 60 mg caffeine + 35 mg CBD

EXPERIMENTAL

Acute administration of oral THC (2.5 mg), oral caffeine (60 mg), and oral CBD (35 mg) three times in study session (Time 0, 60, and 120).

Drug: Oral THC; Drug: Oral CBD; Drug: Oral Caffeine

Interventions

Oral Placebo DRUG

Placebo will be orally self-administered by study participants.

Oral placebo

Oral THC DRUG

THC will be orally self-administered by study participants.

Oral administration of 2.5 mg THC; Oral administration of 2.5 mg THC + 60 mg caffeine; Oral administration of 2.5 mg THC + 60 mg caffeine + 35 mg CBD

Oral CBD DRUG

CBD will be orally self-administered by study participants.

Oral administration of 2.5 mg THC + 60 mg caffeine + 35 mg CBD

Oral Caffeine DRUG

Caffeine will be orally self-administered by study participants.

Oral administration of 2.5 mg THC + 60 mg caffeine; Oral administration of 2.5 mg THC + 60 mg caffeine + 35 mg CBD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Person is between 18 and 55-years-old (inclusive).
• Person has a body mass index (BMI) between 18 and 35 Kg/m\^2 (inclusive).
• Person is willing and able to provide informed consent.
• Person has consumed cannabis products containing THC in the past.
• Person has consumed caffeine products in the past.
• If person uses medication that has been deemed acceptable (e.g., not contraindicated) by the Investigator, the person has maintained a stable dose and regimen on existing medications for at least 30 days prior to participation in the study and throughout the study.
• Person agrees to abide by all study restrictions and comply with all study procedures.

You may not qualify if:

• Person has a known history of significant allergic condition or significant hypersensitivity to cannabis, cannabinoid medications, hemp products, or excipients of the investigational product.
• Person has a known history of significant allergic condition or significant hypersensitivity to caffeine or caffeine products.
• Person has been exposed to any investigational drug or device \< 30 days prior to randomization or plans to take an investigational drug during the study.
• Person has used cannabis, cannabinoid analogue (e.g., dronabinol, nabilone), and/or any CBD- or delta-9-tetrahydrocannabinol (THC)-containing product within 30 days of screening or during the study.
• Person has history of use of any synthetic cannabinoid receptor agonist (e.g., spice, K2) within the past year.
• Person consumes more than 400 mg/day of coffee or other caffeine products (approximately 4 cups of coffee per day) on average within 30 days of screening.
• Person has used illicit substances (e.g., amphetamine, cocaine, methamphetamine, 3,4-Methyl enedioxy methamphetamine \[MDMA\], lysergic acid diethylamide \[LSD\], ketamine, heroin, psilocybin, salvia, prescription medications not prescribed to the person) within 30 days of screening or during the study.
• Person tests positive for any substance, including THC, at screening.
• Person is currently using products or medications that may interact with one or more of the ingredients in the investigational product, including the following drugs or supplements: warfarin, clobazam, valproic acid, phenobarbital, mechanistic target of rapamycin \[mTOR\] inhibitors, oral tacrolimus, St. John's wort, Epidiolex, over the counter stimulants (e.g., phentermine), prescribed stimulants (e.g., Ritalin, Vyvanse), antihypertensive drugs (e.g., captopril, valsartan).
• Person endorses current suicidal intent as indexed via items 4 and 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Person has a history or family history of psychosis or schizophrenia.
• Person has a diagnosis of cardiac disease or significant cardiac condition.
• Person has a diagnosis of hypertension and/or a blood pressure reading with systolic pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg.
• Person has an acute or progressive disease or disorder that is likely to interfere with the objectives of the study or the ability to adhere to protocol requirements.
• Person is currently pregnant, breastfeeding, or is planning to become pregnant within 30 days of completing the study.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Canopy Growth Corporation: collaborator

Study Sites (1)

Johns Hopkins University School of Medicine BPRU

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Interventions

Dronabinol; Caffeine

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Justin Strickland, Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: July 28, 2022
• Study Start: January 20, 2023
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: October 8, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)