None listed
Conditions
Brief summary
Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it is possible that an alternative, more pragmatic, approach lies in psychedelic ‘microdosing’. Microdosing refers to repeated administration of psychedelics such as LSD or psilocybin in doses around the threshold for overtly altering perception. The purpose of this study is to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing Psychedelic-Microdose Assisted – Meaning-Centred Psychotherapy (PA–MCP) to standard Meaning-Centred Psychotherapy (MCP) in people who have a life-threatening cancer diagnosis and symptoms of anxiety and/or depression. Although MCP is a well-established psychotherapeutic treatment in advanced cancer populations (Breitbart et al., 2010; Breitbart et al., 2012), to date, there has been no research that investigates whether the efficacy and effectiveness of this therapy might be improved if delivered alongside a standardised microdose regimen of a psychedelic compound. Participants with advanced stage cancer and symptoms of anxiety and/or depression (N=40; 20 Maori, 20 non-Maori) will be randomised under double-blind conditions to receive MCP alongside repeated doses of either an LSD microdose (PA–MCP) or inactive placebo. The feasibility, acceptability and safety of this intervention and physiological and psychological measures will be recorded at baseline and after completion of each session of MCP and at a one month and six-month follow-up. Our findings will enable a rigorous evaluation of the feasibility of a larger randomised controlled trial and provide initial indication of potential benefits of psychedelic microdosing for psychological distress in advanced stage cancer patients.
Interventions
Psychedelic-microdose plus Meaning-Centred Psychotherapy (PA–MCP)
Lysergic acid diethylamide (LSD) microdose, starting at 8 mcg (titration protocol) taken 2 times a week for 6 weeks + 1 day, totaling 13 doses. LSD will be dissolved in pharmaceutical solvent to create single use vials each containing up to 15 mcg base LSD equivalent. Doses will be extracted from the vial using a single-use syringe, and administered sublingually.
Implementation of the titration protocol is based on participant
Psychedelic-microdose plus Meaning-Centred Psychotherapy (PA–MCP) Lysergic acid diethylamide (LSD) microdose, starting at 8 mcg (titration protocol) taken 2 times a week for 6 weeks + 1 day, totaling 13 doses. LSD will be dissolved in pharmaceutical solvent to create single use vials each containing up to 15 mcg base LSD equivalent. Doses will be extracted from the vial using a single-use syringe, and administered sublingually. Implementation of the titration protocol is based on participant response, the dose will be reduced by half (if reported to be too much) initially, and then will change by 1 mcg per dose, with a minimum dose of 4 mcg and maximum dose of 12 mcg. A mix of supervised and unsupervised monitored administration. Participants will also receive 7 weekly 1-hour sessions of MCP on days 1, 8, 15, 22 and 29, 36, 43 (+/- 1 day), notwithstanding the potential need for break weeks (see below). The MCP sessions will be conducted at either the research clinic site or via Zoom (in the case the participant is too unwell to travel) by a registered psychologist who has been trained and has expertise in delivering MCP. MCP is an existential therapeutic approach that combines didactic components with experiential exercises to facilitate participants’ understanding and connection to various sources of meaning (Breitbart et al., 2010). The goal of MCP is to have patients understand the concept of meaning and its importance in life, particularly as one faces the ultimate limitation of an impending death. The proposed study will follow the manualised and previously validated 7-week protocol for IMCP in patients with stage IV solid tumour cancers (Breitbart et al., 2018) The schedule and process of dosing is tied to MCP treatment. Dosing will occur in clinic when participants attend each MCP session i.e., days 1, 8, 15, 22, 29, 35, 43 (+/- 1 day). On dosing days between MCP sessions, i.e., days 4, 11, 18, 25, 32, 39 (+/- 1 day), doses will be self-administered at home. This dosing pattern will be repeated for a total of 13 occasions over a 43-day period on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 35, 39, 43 (+/- 1 day). All doses will be administered by 2pm at the latest to minimize potential disruptions to sleep. Participants have a maximum of 7x break-weeks available where they can take a one week break from MCP and medication dosing and would resume participation of the protocol the following week. These may be necessary if a participant is unwell due to their cancer, or cancer treatment, or has other medical commitments. Data will be collected on participant attendance to MCP sessions, and we will keep track of doses taken using a mix of logging in clinic (by study staff) and by participants via the completion of their 'dose day questionnaire'. Furthermore, MCP treatment fidelity (30% of the total MCP sessions) will be assessed by an appropriately trained member of the study team.
Sponsors
The University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Diagnosis with an incurable stage IV solid organ malignancy. - Prognosis of at least 6 months life expectancy from the time of screening. - A score 4 or higher on the distress thermometer. - Agree to have study visits video and/or audio recorded. - Agree to inform the Investigators within 48 hours of any medical conditions and procedures being undertaken. - Willing for the Investigators to communicate directly with their medical team to determine medical suitability for study participation (oncologist, GP, palliative care physician, etc). - Agree to refrain from starting any new psychiatric medication and/or psychotherapy during the study period. - Agree to have transportation other than driving themselves to where they are staying on the days of medication dosing. - Able and willing to be contacted via telephone for all necessary telephone contacts. - Agree to use an effective form of contraception if of child-bearing potential for the duration of medication dosing. - Must provide a contact/support person in the event of the being unreachable by study staff or in the event of severe distress or suicidality. - Proficient in speaking and reading English. - Agree to not use any medications on the prohibited medications list during the course of the study. - Agree not to take any herbal supplement for the duration of medication dosing (except with prior approval of the research team).
Exclusion criteria
- Currently participating in a clinical trial of a systemic anti-cancer treatment - Pregnancy or lactating. - BMI < 18.5. - Diagnosis of cerebral metastases. - Karnofsky performance scores below 50 or other physical limitations that preclude participation in weekly psychotherapy and microdosing of LSD. - Upon review of psychiatric history (i.e., responses to the relevant modules of MINI (Standard version 7.0.2)), participants must not have any current or past diagnosis that would be considered a risk to participation in the study: - Lifetime history of schizophrenia or other psychotic disorders, or bipolar I or II disorder assessed through participant interview. - Or a current diagnosis of PTSD, panic disorder, agoraphobia, OCD, anorexia, and bulimia. - Liver function test >3 times the upper limit of normal or creatinine clearance <30 mL/min. - Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of potential increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm. Participants with other mild, stable chronic medical problems may be enrolled if the site physician, CI, and Study Physician agree the condition would not significantly increase the risk of LSD administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the IMP. Examples of stable medical conditions that could be allowed include, but are not limited to Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), etc. Any medical disorder judged by the investigator to significantly increase the risk of LSD administration by any mechanism would require exclusion. - Blood pressure not exceeding 160 mmHg (systolic) and 90 mmHg (diastolic) (measured at three time-points). - Current serious suicide risk, as determined through psychiatric interview, responses to The Columbia-Suicide Severity Rating Scale (C-SSRS), and clinical judgement of the investigator, however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behaviour, in the judgement of the investigator, will not be enrolled. Any participant presenting with the following on the Baseline C-SSRS will be excluded: - Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more; - Suicidal ideation score of 5 within the last 6 months of the assessment; - Any suicidal behaviour, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behaviour may be included if approved by the Study Physician. - Any lifetime history of psychedelic microdosing; defined as repeated low-dose psychedelic usage for more than a week at a time. - Use of a psychedelic within the last year. - Recent or current use of illicit drugs including methamphetamine, heroin and synthetic cannabis. Other non-prescribed drugs will prompt exclusion at the discretion of the study physician. - Current THC usage will prompt exclusion if the participant does not agree to cease. However, CBD is permitted, and usage will be recorded.
Outcome results
None listed