Exploring The Effect Of Cannabidiol On Cannabis Tolerance Using A Novel Vaporiser Device In Heavy Users (Stage 1) (ENDURANCE)

Exploring The Effect Of Cannabidiol On Cannabis Tolerance Using A Novel Vaporiser Device In Heavy Users: A Randomised Placebo-Controlled Experimental Study (Stage 1)

Cannabis contains delta-9-tetrahydrocannabinol (THC), which causes intoxication. People who use cannabis frequently often develop tolerance, meaning they need to use more THC to feel the same effects. Cannabidiol (CBD) is another compound found in cannabis that is not intoxicating and may influence how THC affects the body and brain.

This study will examine whether taking CBD changes how much THC heavy cannabis users consume to reach their usual level of intoxication. The study will also develop a new laboratory method that allows participants to safely and gradually self-administer THC using a vaporiser, similar to how cannabis is used in real-world settings.

The study will include around 30 adults who use cannabis heavily. In the first stage, participants will take part in pilot sessions to help refine the THC administration procedure. In the second stage, participants will attend two study sessions and receive a single oral dose of CBD or placebo, in a random order. After this, they will inhale THC using a vaporiser and decide when to stop based on how intoxicated they feel.

Researchers will measure how much THC is used, along with mood, mental health symptoms, thinking abilities, physical measures such as heart rate and blood pressure, and blood levels of THC and CBD. The results will help improve understanding of cannabis tolerance and whether CBD alters responses to THC in heavy cannabis users.

Study Overview

• Status: Not yet recruiting
• Conditions: Cannabis Intoxication
• Intervention / Treatment: Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

Detailed Description

Cannabis produces its intoxicating effects mainly through delta-9-tetrahydrocannabinol (THC). People who use cannabis frequently often develop tolerance, meaning they need to consume larger amounts of THC to achieve their usual level of intoxication. Cannabidiol (CBD) is another cannabinoid found in cannabis that does not cause intoxication and may alter how THC affects the body and brain. However, its effects on cannabis tolerance in heavy users are not well understood.

This study aims to develop a controlled laboratory method for measuring cannabis tolerance and to investigate whether CBD changes how much THC heavy cannabis users consume. The study is conducted in two stages and will recruit approximately 30 adult heavy cannabis users who do not have a history of psychotic or major medical disorders.

In Stage One, participants will take part in pilot sessions to establish a safe and reliable method of THC administration using a handheld vaporiser. Participants will self-administer THC in small doses at regular intervals and decide when they have reached their usual and maximum tolerated levels of intoxication. These pilot sessions will be used to refine the timing, dosing, and outcome measures used in the main experiment.

In Stage Two, participants will complete two experimental sessions in a double-blind, randomised, placebo-controlled, crossover design. In each session, participants will receive a single oral dose of CBD (1000 mg) or a matching placebo, followed three hours later by THC administration using the vaporiser. The order of CBD and placebo will be randomised, and sessions will be separated by a washout period.

During each experimental session, participants will self-titrate THC intake until they reach their typical desired level of intoxication and may continue until they reach their maximum tolerated level. Cannabis tolerance will be assessed by measuring the amount of THC consumed, based on changes in vaporiser cartridge weight and the number of inhalations required to reach these intoxication levels.

Additional outcomes include subjective drug effects, mood, psychotic-like symptoms, cognitive performance, speech measures, physical observations (such as heart rate and blood pressure), and blood levels of THC, CBD, and related biomarkers. Safety will be closely monitored throughout all sessions by trained medical staff.

The findings from this study will help establish a novel experimental model of cannabis tolerance and improve understanding of how CBD influences responses to THC in heavy cannabis users.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edward Chesney, MRCPsych PhD; Phone Number: +4420 7836 5454; Email: kingscrf@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • King's Clinical Research Facility
    • Contact: Edward Chesney; Phone Number: +4420 7836 5454

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults, between 18 and 45 years old
2. Heavy and frequent cannabis user: using 7-14 grams of high potency cannabis per week over the past month, and using cannabis on at least 5 days per week over the past month
3. Positive urine drug screen (UDS) for cannabis
4. Willing to abstain from cannabis use for 4 hours before any experimental session.
5. Willing to eat two non-vegan full-fat yoghurts to aid drug absorption
6. Providing written informed consent.

Exclusion Criteria:

1. Dependent use of alcohol or illicit drugs (apart from cannabis or tobacco/nicotine)
2. Not able to provide a UDS which is negative for illicit drugs (apart from cannabis)
3. Not able to provide a negative alcohol breath test
4. Personal or family history (first-degree) of psychosis or mania
5. Currently prescribed antidepressant, mood-stabilising, antipsychotic or stimulant medication, or regular medication for a significant medical condition (e.g. antihypertensives, anticonvulsants, anticoagulants, or immunosuppressants)
6. Diagnosis of a major medical or psychiatric illness that the study doctor considers inappropriate for the purposes of this study
7. Female participants who are pregnant or mothers who are lactating
8. Not willing to use an adequate form of contraception for the duration of the study
9. Participant in another experimental medicine study or clinical trial within the past three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delta-9-tetrahydrocannabinol/Cannabidiol; Delta-9-tetrahydrocannabinol/Cannabidiol (vaporised; self-administered by the participant, titrated to individual tolerability)	Drug: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD); Vida T400:C20 Blueberry Cookies Medical Cannabis Cartridge (400mg delta-9-tetrahydrocannabinol and 20mg cannabidiol per cartridge)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cannabis tolerance	Change in THC cartridge weight	From initiation of use until the participant reaches their desired level of intoxication (self-titrated), assessed up to 4 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cannabis tolerance (maximum)	Change in THC cartridge weight	From initiation of use until the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Drug effects questionnaire (DEQ)	Five-item questionnaire on drug effects	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Visual analogue scales	Relaxed/Anxious; Sad/Happy; Not paranoid/Paranoid; Thinking clearly/confused; Tired/Energetic	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Observer Rated Cannabis Intoxication Scale (ORCIS)	A Likert scale to rate the participant's level of intoxication	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Cannabis withdrawal Scale (CWS)	A 19-item self-report questionnaire designed to assess the severity of cannabis withdrawal symptoms	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Marijuana Craving Questionnaire-Short Form	A brief assessment tool used to measure craving for cannabis	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Positive and negative symptom scale	An investigator-rated measure of psychotic symptoms.	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Psychotomimetic States Inventory	A 48-item questionnaire that was developed for use in drug studies to measure psychotic-like experiences	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Digit symbol substitution test		Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.
Forward and reverse digit span	Assessment of working memory: Forward Digit Span is the maximum number of digits the participant can correctly repeat in the same order, and Reverse Digit Span is the maximum number of digits the participant can correctly repeat in reverse order.	Baseline; The timepoint at which the participant reaches their desired level of intoxication (self-titrated); The timepoint at which the participant reaches their maximum tolerated level of intoxication (self-titrated), assessed up to 4 hours.

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: South London and Maudsley NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 30, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Cannabis; THC; Delta-9-tetrahydrocannabinol
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol; Dronabinol
• Other Study ID Numbers: R&D2025/050

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