Acceptability of cannabidiol as a treatment for people at clinical high risk for psychosis

A survey of 55 individuals at clinical high risk for psychosis found that cannabidiol (CBD) is a highly acceptable treatment option, with most participants familiar with the compound, willing to use it, and anticipating fewer side effects compared to existing medications.

The Gist

Imagine you are standing at a crossroads. On one path, there is a foggy, uncertain future where things might get scary and confusing (this represents the "clinical high risk" for psychosis, a state where someone shows early warning signs of a mental health crisis but hasn't fully crossed the threshold yet). On the other path, there are signposts pointing toward help, but many of the traditional signs are worn out, confusing, or come with heavy baggage.

This research paper is like a group of travelers (55 young people) gathering at that crossroads to ask a simple question: "If we could try a new, lighter backpack called CBD, would we be willing to carry it?"

Here is the story of their journey, broken down into simple parts:

1. The Problem: The "Empty Toolbox"

For a long time, doctors have had a difficult job. When someone is showing early warning signs of psychosis, there are very few approved medicines to help them. The existing tools (like traditional antipsychotic medications) are powerful, but they often come with heavy side effects—like a backpack filled with bricks that makes you gain weight, feel sluggish, or feel awkward. Because of this, many people are hesitant to use them.

2. The New Candidate: The "Lightweight Backpack" (CBD)

Enter CBD (Cannabidiol). Think of CBD as a new type of backpack. It comes from the cannabis plant, but it's the "good" part that doesn't get you high. It's already popular in health stores, and people know it generally as something gentle and natural.

The researchers wanted to know: If we offered this lightweight backpack to people at the crossroads of early mental health risks, would they want to try it?

3. The Survey: Asking the Travelers

The researchers asked 55 young people (mostly in their mid-20s) to fill out a survey. They didn't just ask "Do you want this?"; they asked deeper questions:

• Familiarity: "Have you heard of this?" (91% said yes).
• Experience: "Have you tried it before?" (About half had tried over-the-counter CBD).
• Willingness: "If you were struggling, would you take this?"

The Result: A massive 75% said, "Yes, I'd give it a try!"

4. Why They Liked It: The "Less Scary" Factor

Why was the answer so positive?

• Fewer "Bricks": The travelers believed this new backpack would have fewer heavy side effects (like weight gain or feeling like a zombie) compared to the old, heavy medications.
• Less Stigma: Taking a pill that looks like a vitamin feels less "medical" and less stigmatizing than taking a strong psychiatric drug. It feels more like a natural supplement.
• The "Cannabis" Hurdle: Some people were worried because CBD comes from the cannabis plant. However, the study found that even people who had never used cannabis before were still willing to try CBD. The "natural" label seemed to outweigh the fear of the plant connection.

5. What They Wanted It to Fix

When asked what they hoped CBD would help with, the travelers didn't just want to stop the "fog" of psychosis. They wanted relief from the daily annoyances:

• Anxiety (The #1 request)
• Sleep problems
• Mood swings

It's as if they were saying, "We don't just want to stop the storm; we want to feel calm and sleep well tonight."

6. The Shape of the Backpack

The researchers also asked, "How do you want to carry this?"

• The Verdict: Most people preferred a tablet or a capsule (like a normal pill).
• The Catch: Currently, the only legal, approved version of CBD is an oil (a liquid you have to measure out).
• The Takeaway: People are used to popping a pill. If scientists want to make CBD a standard treatment, they might need to invent a pill version, because people aren't excited about drinking oil.

7. The Bottom Line

This study is like a "vibe check" before building a new bridge. The researchers found that the people who need help the most are actually very open to trying CBD. They see it as a friendly, less scary option compared to the heavy medications of the past.

The Caveat: Just because they say they want to try it doesn't mean they will stick with it for years (adherence is a different story). Also, this was just a survey; we still need to prove it actually works to stop the psychosis.

In a nutshell: The people at the front line of mental health risk are ready and willing to try CBD. They see it as a lighter, friendlier, and less scary way to navigate their journey, provided it comes in a convenient pill form.

Technical Summary

1. Problem Statement

• Clinical Gap: There are currently no licensed pharmacological interventions for individuals at Clinical High Risk for Psychosis (CHR-P). Approximately 20% of CHR-P individuals transition to full psychosis within two years.
• Limitations of Current Care: Meta-analyses indicate no robust evidence that existing pharmacological or psychological interventions are superior to needs-based care in preventing transition or reducing attenuated positive symptoms.
• The Candidate: Cannabidiol (CBD) has shown promise in reducing psychotic symptoms in established psychosis and CHR-P populations, with a favorable safety profile compared to antipsychotics (which often cause weight gain, sedation, and sexual dysfunction).
• The Research Question: While CBD is known to be acceptable to patients with established psychosis, its acceptability among the specific, vulnerable population of CHR-P individuals has not been formally assessed. Understanding patient willingness, expectations, and formulation preferences is critical for designing future clinical trials and implementing preventive strategies.

2. Methodology

• Study Design: Cross-sectional survey study embedded within a larger digital screening program (ENTER).
• Participants:
  • Sample Size: $N = 55$ CHR-P individuals (mean age 24.3 years; 69% female).
  • Recruitment: Individuals aged 12–35 recruited via social media, flyers, and university newsletters in the UK (London, Glasgow) and Italy (Pavia).
  • Inclusion Criteria: Scored $\ge$6 on the Prodromal Questionnaire 16-item (PQ-16) and confirmed CHR-P status via the Comprehensive Assessment of At-Risk Mental States (CAARMS) interview.
• Data Collection:
  • Participants completed a 15-item interview-based questionnaire.
  • Domains Assessed: Prior experience with cannabis/CBD, willingness to try CBD, expected efficacy, anticipated side effects, and formulation preferences.
  • Comparators: Participants ranked CBD against other interventions (antipsychotics, antidepressants, anti-anxiety meds, talking therapies) and compared side effect profiles against current medications.
• Statistical Analysis:
  • Primary analysis restricted to CHR-P participants.
  • Used Fisher's exact test for demographic/clinical associations (due to small sample sizes).
  • Used pairwise Wilcoxon signed-rank tests with Holm continuity correction for intervention preference rankings.
  • Significance threshold: $p < 0.05$.

3. Key Contributions

• First Acceptability Assessment in CHR-P: This is the first study to formally quantify the acceptability of CBD specifically within the CHR-P population, a group for whom no approved pharmacological treatment exists.
• Long-term Feasibility: The study assesses not just initial willingness but the duration of treatment participants are willing to undertake, which is crucial for preventive trials (typically requiring 1–2 years of intervention).
• Formulation Preferences: It identifies specific preferences for delivery methods (tablets/capsules vs. oils), addressing a gap between current approved formulations (oils) and patient preference.
• Transdiagnostic Perspective: The findings suggest CBD is viewed as a treatment for general distress (anxiety, sleep, mood) rather than solely for psychotic symptoms, supporting its potential as a transdiagnostic early intervention.

4. Key Results

• High Acceptability:
  • 75% of CHR-P participants were willing to take CBD as an intervention for mental health problems.
  • 76% were willing to consider CBD specifically.
  • Among those willing, 62% were prepared to take it for two years or more, aligning with the critical risk window for psychosis onset.
• Demographic Correlates:
  • Willingness was high across all demographics.
  • No significant differences were found based on gender, ethnicity, or prior cannabis use.
  • Interestingly, prior use of over-the-counter CBD did not significantly increase willingness ($p=0.20$), though 87% of prior users were willing to try it again.
• Expectations of Efficacy and Safety:
  • 74% believed CBD would improve symptoms; only 2% feared it would worsen them.
  • 73% believed CBD would have more tolerable side effects than their current medications (antidepressants/anti-anxiety drugs).
  • 44% believed CBD would have no side effects.
• Ranking of Interventions:
  • CBD was ranked significantly higher (more acceptable) than antipsychotics (median rank 3 vs. 5, $p<0.001$).
  • CBD was statistically comparable in acceptability to talking therapies, antidepressants, and anti-anxiety medications.
• Target Symptoms: Participants primarily wanted CBD to address anxiety (77%), followed by sleep problems (50%) and mood dysfunction (40%).
• Formulation Preferences:
  • Preferred: Tablets (35%) and Capsules (28%).
  • Least Preferred: Liquids/Oils (13%).
  • Note: 77% were willing to take capsules and 73% tablets, despite the current approved formulation being an oil.

5. Significance and Implications

• Trial Design: The high willingness to engage in long-term treatment (2+ years) supports the feasibility of conducting large-scale, longitudinal preventive trials of CBD in CHR-P populations.
• Clinical Framing: The data suggests that framing CBD as a treatment for anxiety, sleep, and mood (transdiagnostic symptoms) rather than solely as an antipsychotic may increase engagement and adherence.
• Product Development: The strong preference for solid formulations (tablets/capsules) over oils highlights a need for pharmaceutical development to create alternative CBD delivery systems that align with patient preferences and current regulatory approvals.
• Stigma Reduction: The high acceptability, even among those with reservations about cannabis, suggests CBD may be a less stigmatized entry point for treatment compared to traditional antipsychotics.
• Limitations: The study acknowledges limitations including a modest sample size ($N=55$), cross-sectional design (measuring prospective rather than actual adherence), and geographic restriction to the UK and Italy, which may limit generalizability to regions with different cannabis legislation.

Conclusion: CBD is perceived as a highly acceptable, safe, and effective potential intervention by young people at clinical high risk for psychosis. The findings provide a strong rationale for proceeding with long-term randomized controlled trials to evaluate its efficacy in preventing the onset of psychosis.