Study on Regulated Cannabis Sales in Pharmacies (SCRIPT)

The Safer Cannabis - Research In Pharmacies Randomized Controlled Trial (SCRIPT)

Though regulated cannabis sales are increasing, little is known about the individual health effects of cannabis regulation. Data from countries with a regulated market can be used to test the effect of regulation on the price of cannabis in the illicit market, and to explore its effect on social and health outcomes at the societal level, but strength of evidence for individual health and social outcomes is more limited because it must be aggregated on a state or country level. Data on individual and social outcomes should include baseline measurements before and outcome measurements after regulations changed. In this context, randomized-controlled trials are the least biased source of data on the effects of interventions.

The SCRIPT study aims to investigate the individual health and social impact on recreational cannabis users who are allowed to purchase authorized, regulated cannabis from Swiss pharmacies compared to users who buy cannabis on the illicit market. Participants are randomly allocated in one of the two groups and followed-up for 6 months. After 6 months, all participants are allowed to participate in the intervention and the cohort is followed up for another 18 months.

The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles.

The SCRIPT study adheres to rigorous quality criteria for the production and storage of regulated cannabis products. Only vaping / vaporizing electronic devices which are validated to reduce exposure to toxicants compared to cannabis smoking are recommended.

Study Overview

• Status: Recruiting
• Conditions: Cannabis; Cannabis Use; Marijuana Smoking
• Intervention / Treatment: Drug: Regulated cannabis from authorized pharmacies; Drug: Cannabis from the illicit market

Detailed Description

Cannabis is the most consumed illegal substance in Switzerland. Many countries and an increasing number of US states have regularized cannabis production and distribution for non-medical use. Analyses of the effects of regulation are promising on a population level, but the causal effects of regulation have only been assessed in before-after studies or ecological comparisons between countries or states. Randomized controlled trials (RCT) are needed to better assess the effects of cannabis regulation on individuals. Since May 2021, the conduct of scientific pilot studies are allowed in Switzerland. While rigorous quality and safety standards cannot be implemented in illicit production and distribution networks, they can be implemented in regulated markets. Beyond psychiatric outcomes, the major hazard associated with cannabis use on somatic health outcomes are mostly related to smoking cannabis and mixing it with tobacco. Regulation therefore also opens the door to harm reduction strategies like counseling users to vape, vaporize, or eat cannabis instead of smoking it. Regulated sale in pharmacies would further facilitate smoking cessation counseling and access to health and social care for those in need. The SCRIPT trial aims to investigate the individual health and social impact on recreational cannabis users who are offered a multimodal intervention of authorized, regulated cannabis sale in combination with counselling on reducing harm (intervention group) compared to users who continue to buy cannabis on the illicit market (control group).

The intervention group is allowed to purchase regulated cannabis in authorized pharmacies. The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles. The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market.

This is a multicenter, pragmatic, open-labelled randomized controlled trial from baseline to 6-months follow-up. After 6 months, the control group is allowed to purchase cannabis in pharmacies, too, and the study designs changes to a cohort-study.

• Study Type: Interventional
• Enrollment (Estimated): 1091
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Reto Auer, Prof.; Phone Number: +41 31 684 58 79; Email: reto.auer@unibe.ch
• Study Contact Backup: Name: Kathrin Bieri; Phone Number: +41 31 684 42 83; Email: kathrin.bieri@unibe.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3012
    • Recruiting
    • University of Bern
  • Lucerne, Switzerland
    • Recruiting
    • Zentrum für Hausarztmedizin und Community Care, University of Lucerne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• At least 18 years old (validated with valid identification document)
• Written informed consent
• Regular cannabis user: Self-reported cannabis use at least once a month over the last 6 months and verified cannabis exposure based on urine analysis at baseline
• Resident status in the canton of Bern (for cannabis purchase in the cities of Bern or Biel) or in the city of Lucerne (for cannabis purchase in the city of Lucerne) (validated with registration confirmation from the municipality or confirmation of the residential address)

Exclusion Criteria:

• Pregnant women (pregnancy test based on urine sample)
• Breastfeeding women (self-reported)
• People with a prescription for medical cannabis (self-reported)
• People currently in psychiatric inpatient treatment (self-reported)
• People with current, severe psychosis (self-reported and confirmed by study nurse/study physician)
• People with current, severe suicidal thoughts (self-reported and confirmed by study nurse/study physician)
• Inability to follow the procedures of the study due to severe cognitive impairment or language problems
• People who cannot attend the baseline study visit in-person
• People planning to move out of the canton of residence within 6 months of entering the trial.
• People who are participating or have participated (inclusion date up to one year ago) in another cannabis pilot trial which allows to buy regulated cannabis (validated by matching untraceable codes between studies witch the same catchment area).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regulated cannabis from authorized pharmacies (intervention group); Multimodal intervention of authorized, regulated cannabis sale in combination with counselling on reducing harms for recreational cannabis users in Swiss pharmacies (intervention group).	Drug: Regulated cannabis from authorized pharmacies; The intervention group is allowed to purchase regulated cannabis in authorized pharmacies. The intervention includes various offers: Participants can choose between cannabis sorts and delivery methods, and they are encouraged to shift from smoking cannabis to vaping cannabis-containing e-liquids, vaporizing cannabis blossoms or using oral cannabis. Vaping / vaporizing electronic devices are also recommended. At the same time, pharmacists offer opportunistic smoking cessation and problematic cannabis, alcohol use and further drug use counseling that conforms to motivational interviewing principles. Study participants can choose between different cannabis-containing products such as dried cannabis flowers, cannabis concentrates (colloquially called hashish or hash), e-liquids and oral cannabis. Besides the cannabis products, participants can buy vaping or vaporizing electronic devices at the pharmacy (they are not considered as study products).
Active Comparator: Cannabis from the illicit market (control group); The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market.	Drug: Cannabis from the illicit market; The control group receives no intervention and is expected to continue purchasing cannabis from the illicit market.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported cannabis and tobacco smoking abstinence in the 7 days prior to the 6-months follow-up visit, validated by carbon monoxide (CO) in exhaled air	To distinguish between non-smoker and smoker, the cut-off for the CO measurement is <10 parts per million (ppm) and no self-reported combustible cannabis and tobacco use within the last 7 days (7-day point prevalence of abstinence). The validation is based on the worst-case principle. Smokers are considered as; participants with a positive CO measurement, even if the self-report is negative.; participants with a positive self-declaration, even if the CO measurement is negative.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of toxicants in urine	Measured in urine from a sub-sample	6 months
Type of cannabis sold per participant in pharmacies		6, 12, 18, & 24 months
Amount of cannabis sold per participant in pharmacies		6, 12, 18, & 24 months
Self-reported cannabis purchase on the illicit market		6, 12, 18, & 24 months
Self-reported frequency of use		6, 12, 18, & 24 months
Concentration of THC and CBD in cannabis bought on the illicit market	Measured in cannabis from a random sub-sample.	6 months
Concentration of contaminants in cannabis bought on the illicit market	Measured in cannabis from a random sub-sample.	6 months
Severity of generalised anxiety disorder	Recorded as participant-reported outcome. Measured by Generalised Anxiety Disorder (GAD-7) questionnaire (scores range from 0 to 21, with higher scores indicating higher levels of generalised anxiety)	6, 12, 18, & 24 months
Attention Deficit Hyperactivity Disorder (ADHD) symptoms in adults	Recorded as participant-reported outcome. Measured by Adult ADHD Self-Report Scale (ASRS) questionnaire.	6, 12, 18, & 24 months
Severity of depression	Recorded as participant-reported outcome. Measured by the Patient Health Questionnaire-9 (PHQ-9) (scores range from 0 to 27, with higher scores indicating more depressive symptoms)	6, 12, 18, & 24 months
Number of psychotic symptoms	Recorded as participant-reported outcome. Measured by the Psychotic Symptoms (PS) Checklist	6, 12, 18, & 24 months
Somatic health	Recorded as participant-reported outcome. Measured by Pittsburgh Sleep Quality Index (PSQ-I) questionnaire.	6, 12, 18, & 24 months
Impact of COPD	Recorded as participant-reported outcome. Measured by COPD Assessment Test (CAT) questionnaire (scores range from 0 to 40, with higher scores indicating indicating a more severe impact of COPD on a patient's life).	6, 12, 18, & 24 months
Severity of dyspnea	Recorded as participant-reported outcome. Measured by Modified Medical Research Council (MMRC) scale for dyspnea.	6, 12, 18, & 24 months
COPD exacerbation assessment	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Quality of life (health-related)	Recorded as participant-reported outcome. Measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire.	6, 12, 18, & 24 months
Perception of stress	Recorded as participant-reported outcome. Measured by the Perceived Stress Scale (PSS).	6, 12, 18, & 24 months
Cannabis use and purchase behavior	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Cannabis use disorder	Recorded as participant-reported outcome. Measured by Cannabis Use Disorders Identification Test - Revised (CUDIT-R) questionnaire.	6, 12, 18, & 24 months
Consumption motives	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Consumption competence	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Consumption risk perception	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Nicotine/tobacco use behavior	Recorded as participant-reported outcome	6, 12, 18, & 24 months
Exposure to second-hand smoke	Recorded as participant-reported outcome	6, 12, 18, & 24 months
Alcohol consumption behavior	Recorded as participant-reported outcome. Measured by Alcohol Use Disorders Identification Test (AUDIT-C).	6, 12, 18, & 24 months
Drug consumption behavior	Recorded as participant-reported outcome. Measured by Alcohol, Smoking and Substance Involvement Screening Test (ASSIST V3.0).	6, 12, 18, & 24 months
Medication use behavior	Recorded as participant-reported outcome	6, 12, 18, & 24 months
Treatment/Counseling Experience	Recorded as participant-reported outcome	6, 12, 18, & 24 months
Use of health and social services	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Body mass index	Cardiovascular risk factor (CVRF) measured at physical examinations.	6 months
Blood pressure	Cardiovascular risk factor (CVRF) measured at physical examinations.	6 months
Waist-to-hip ratio	Cardiovascular risk factor (CVRF) measured at physical examinations.	6 months
Number of safety events	Recorded as participant-reported outcome.	6, 12, 18, & 24 months
Inflammation-related protein biomarkers	Measured from blood samples from a sub-sample. Analysis of 92 protein biomarkers associated with inflammatory and immune response processes using the Olink® Target 96 Inflammation Panels.	6 months
Self-reported reported 7-days point prevalence abstinence from cannabis and tobacco smoking at 6 months follow-up, without validation by CO in exhaled air.	Based on interviews by phone or online	12, 18, & 24 months
Shift from smoking to safer, alternative delivery methods of cannabis and, if applicable, tobacco.	Shift from smoking cannabis to safer, alternative delivery methods of cannabis and, if applicable, from smoking tobacco to alternative nicotine delivery systems or nicotine cessation between groups among those who were smoking cannabis at baseline and/or were smoking tobacco at baseline, with and without validation	6, 12, 18, & 24 months

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: Universität Luzern
• Investigators: Study Chair: Reto Auer, Prof., Institute of Primary Health Care (BIHAM), Faculty of Medicine, University of Bern

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cannabis; Cannabinoids; Cannabis sativa; Cannabis Use
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Marijuana Use
• Other Study ID Numbers: SCRIPT

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