Comparative Pharmacokinetic and Pharmacodynamic Effects of Delta-8 and Delta-9 THC

The current study will investigate the subjective, physiological, and cognitive performance effects of inhaled and orally ingested Delta-8 tetrahydrocannabinol (THC) in comparison to both placebo and Delta-9 THC. The purpose of this study is to assess the effects of Delta-8 THC as compared to placebo and Delta-9 THC. Oral fluid, urine, blood, and hair specimens will be collected from participants.

Study Overview

• Status: Completed
• Conditions: Behavioral Pharmacology of Cannabis
• Intervention / Treatment: Drug: Oral Placebo; Drug: Oral Delta-8-THC Cannabis; Drug: Oral Delta-9-THC Cannabis; Drug: Vaporized Placebo; Drug: Vaporized Delta-8-THC Cannabis; Drug: Vaporized Delta-9-THC Cannabis

Detailed Description

The current study will investigate the subjective, physiological, and cognitive performance effects of inhaled and orally ingested Delta-8 THC in comparison to both placebo and Delta-9 THC. Delta-8 THC is an cannabinoid that has become widely available for retail sale in the US due to a loophole in the 2018 Farm Bill. Delta-8 THC is an isomer of Delta-9 THC, which is the compound responsible for most of the psychoactive effects associated with cannabis. Prior research, while limited, has indicated that Delta-8 THC is less potent but has comparable pharmacodynamic effects to Delta-9 THC, especially at higher doses. The purpose of this study is to assess the effects of Delta-8 THC as compared to placebo and Delta-9 THC. Oral fluid, urine, blood, and hair specimens will be collected from participants. The investigators will recruit healthy participants between the ages of 18 and 45 who have prior experience using THC but have not used in at least one month. Two sub-studies will be run, with 5 conditions in each study; sub-study 1 will examine the effects of vaporized Delta-8 THC and sub-study 2 will assess the effects of orally ingested Delta-8 THC. Participants can complete both sub-studies but it is not required. There will be a minimum of 5 outpatient drug administration sessions for each participant, with the option to complete 5 more if interested. The investigators will recruit and consent up to 70 participants in order to obtain 20 completers (up to 40 total individuals) for each sub-study.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Behavioral Pharmacology Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Have provided written informed consent
2. Be between the ages of 18 and 45
3. Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
4. Test negative for recent cannabis use in urine at the screening visit and again upon admission for each experimental session
5. Test negative for other drugs of abuse, including alcohol at the screening visit and upon arrival for each experimental session
6. Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission.
7. Have a body mass index (BMI) in the range of 19 to 36 kg/m2
8. Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg
9. Report prior experience inhaling cannabis (either via smoking or vaporization).
10. Have not donated blood in the prior 30 days.

Exclusion Criteria:

1. Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine in the month prior to the Screening Visit;
2. History of or current evidence of significant medical or psychiatric illness judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures.
3. Use of an over-the-counter (OTC), systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
4. Use of a prescription medication (with the exception of birth control prescriptions) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject. This includes any medication metabolized via CYP2D6, CYP2C9, CYP2B10, or which induce/inhibit CYP3A4 enzymes.
5. Use of any hemp, cannabis or cannabinoid product in the past 3 months.
6. History of xerostomia (dry mouth), or the presence of mucositis, gum infection or bleeding, or other significant oral cavity disease or disorder that in the investigator's opinion may affect the collection of oral fluid samples.
7. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina).
8. Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
9. Epilepsy or a history of seizures.
10. Individuals who have a recent history of traumatic brain injury diagnosed by CT/MRI and have current sequela from prior brain injury, as determined by the study physician.
11. Individuals with anemia judged by medical staff to place the person at risk due to the frequency and volume of blood collected during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Oral Cannabis; Single acute administration of placebo cannabis baked into a brownie	Drug: Oral Placebo; Placebo will be orally self-administered by study participants
Placebo Comparator: Placebo Vaporized Cannabis; Single acute administration of placebo cannabis via commercial vaporizer	Drug: Vaporized Placebo; Placebo will be self-administered by study participants using a vaporizer
Experimental: Oral administration of 10mg D-8-THC; Single acute administration of cannabis containing 10mg Delta-8-THC baked into a brownie	Drug: Oral Delta-8-THC Cannabis; Delta-8-THC cannabis will be orally self-administered by study participants; Other Names: marijuana
Experimental: Oral administration of 20mg D-8-THC; Single acute administration of cannabis containing 20mg Delta-8-THC baked into a brownie	Drug: Oral Delta-8-THC Cannabis; Delta-8-THC cannabis will be orally self-administered by study participants; Other Names: marijuana
Experimental: Oral administration of 40mg D-8-THC; Single acute administration of cannabis containing 40mg Delta-8-THC baked into a brownie	Drug: Oral Delta-8-THC Cannabis; Delta-8-THC cannabis will be orally self-administered by study participants; Other Names: marijuana
Experimental: Oral administration of 20mg D-9-THC; Single acute administration of cannabis containing 20mg Delta-9-THC baked into a brownie	Drug: Oral Delta-9-THC Cannabis; Delta-9-THC cannabis will be orally self-administered by study participants; Other Names: marijuana
Experimental: Administration of vaporized 10mg D-8-THC; Single acute administration of placebo cannabis containing 10mg Delta-8-THC via commercial vaporizer	Drug: Vaporized Delta-8-THC Cannabis; Delta-8-THC cannabis will be self-administered by study participants using a vaporizer; Other Names: marijuana
Experimental: Administration of vaporized 20mg D-8-THC; Single acute administration of placebo cannabis containing 20mg Delta-8-THC via commercial vaporizer	Drug: Vaporized Delta-8-THC Cannabis; Delta-8-THC cannabis will be self-administered by study participants using a vaporizer; Other Names: marijuana
Experimental: Administration of vaporized 40mg D-8-THC; Single acute administration of placebo cannabis containing 40mg Delta-8-THC via commercial vaporizer	Drug: Vaporized Delta-8-THC Cannabis; Delta-8-THC cannabis will be self-administered by study participants using a vaporizer; Other Names: marijuana
Experimental: Administration of vaporized 20mg D-9-THC; Single acute administration of placebo cannabis containing 20mg Delta-9-THC via commercial vaporizer	Drug: Vaporized Delta-9-THC Cannabis; Delta-9-THC cannabis will be self-administered by study participants using a vaporizer; Other Names: marijuana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported Drug Effect ratings on the Drug Effect Questionnaire (DEQ)	Subjective drug effect ratings (0-100) will be collected with the Drug Effect Questionnaire, with 0 being no effect and 100 being maximum effect.	Within 8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate (beats/minute) will be measured while sitting down using the vitals machine.	Within 8 hours
Divided Attention as assessed by the DAT	Divided Attention Task (DAT), cognitive task administered on the computer to assess divided attention.	Within 8 hours
Digit Symbol Substitution Task (DSST) score	Digit Symbol Substitution Task, cognitive task administered to assess response speed, sustained attention, visual spatial skills and set shifting.	Within 8 hours
Paced Auditory Serial Addition Task (PASAT) score	Paced Auditory Serial Addition Task, cognitive task that measures cognitive function by assessing auditory information processing speed and flexibility, as well as calculation ability.	Within 8 hours
Quantitative levels of D-8-THC in blood	Blood is collected through an intravenous catheter, quantitative results are reported in nanograms per milliliter (ng/ml).	Within 8 hours
Quantitative levels of D-9-THC in blood	Blood is collected through an intravenous catheter, quantitative results are reported in nanograms per milliliter (ng/ml).	Within 8 hours
Behavioral task performance as assessed by the DRUID app	Composite score on the DRUID App, a measure of behavioral task performance (range 0-100) where lower scores indicate better performance.	Within 8 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Substance Abuse and Mental Health Services Administration (SAMHSA)
• Investigators: Principal Investigator: Ryan Vandrey, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Actual): August 8, 2024
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; nabiximols
• Other Study ID Numbers: IRB00321661

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No