Ignite Creation Date:
2024-05-06 @ 4:07 PM
Last Modification Date:
2024-10-26 @ 2:04 PM
Study NCT ID:
NCT04882839
Status:
NOT_YET_RECRUITING
Last Update Posted:
2022-09-21
First Post:
2021-04-08
Brief Title:
Evaluating the Feasibility Safety and Efficacy of Psychotherapy Assisted Psilocybin for Treatment of Severe OCD
Sponsor:
Beersheva Mental Health Center
Organization:
Beersheva Mental Health Center
Study Overview
Official Title:
Open Label Phase 1 Study for Evaluating the Feasibility Safety and Efficacy of Psychotherapy Assisted Psilocybin for Treatment of Severe OCD
Status:
NOT_YET_RECRUITING
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Obsessive-compulsive disorder OCD is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety accompanied by repetitive behaviors or mental rituals Individuals with OCD often have diminished quality of life and functional impairment The disorder cause high personal societal and economic costs Current available treatments for OCD show moderate response rate and high rate of symptom relapse The purpose of the current study is to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients Specifically The aim of this study is to investigate the feasibility safety and efficacy of psychotherapy assisted psilocybin for treatment of severe OCD Previous research has shown safety of treatment and high efficacy in reduction of anxiety and depression symptoms However only one study has evaluated the use of psilocybin for OCD patients The protocol includes 15 therapeutic sessions of which 12 are one-hour sessions for psychological preparation and integration and three are eight hours experiential sessions under the influence of psilocybin The research will include 15 participants diagnosed with severe OCD with at least one treatment failure Assessments will be based on comparing ratings of the main outcome measure Y-BOCS at baseline at the middle and at end of treatment Other assessments will include data on side effects- to evaluate safety and possible spiritual variables underlying change in symptoms via standardized questionnaires
Detailed Description:
Background and research rationale
Obsessive-compulsive disorder OCD is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety accompanied by repetitive behaviours or mental rituals performed to control or alleviate this anxiety Individuals with OCD often have diminished quality of life functional impairment and cause substantial caregiver burden and personal and societal economic costs Lifetime prevalence of OCD ranges between 19-25 with patients often not responding to the offered pharmacological or psychological treatment and in extreme cases may even undergo neurosurgical interventions
There are several possible physiological mechanisms leading to the development of OCD which may indicate several possible effective treatment options Nowadays there is a consensus that the dopaminergic and serotonergic pathways are central to the development of the disorder with the basal ganglia as the main area of its origin Other brain areas involved in OCD are the orbitofrontal cortex and anterior cingulate cortex which are connected to the basal ganglia and are involved in regulating attention and awareness Abnormal activity between these areas and other subcortical areas might explain why normally unconscious information processing becomes consciousness and requires additional resources for its regulation It has also been suggested that the aversive emotional activity anxiety fear disgust experienced in OCD relates to hyperactivity in the amygdala The momentary relief brought on by the compulsive behaviour forms a positive feedback which perpetuate the disorder
The gold standard of care for OCD today is a combination of selective serotonin reuptake inhibitors SSRIs and cognitive behavioural therapy CBT Most patients will experience at least some symptomatic relief with these interventions however relapse of symptoms occur in 40-60 of patients and around 25 of patients are unresponsive to treatment Other existing treatments either pharmacological or neurosurgical possess a higher risk for serious side effects It is important to note that even for those patients who are responsive to treatment there are still significant residual impairing symptoms It thus seems that there is a real and immediate need to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients with lower risk and fewer side effects
A new and promising prospect of treatment in mental health is the use of psychedelic substances which interact with the serotonergic pathways and induce a powerful subjective experience with the potential for psychological transformation Specifically psilocybin has received attention in research as a promising alternative in the treatment of severe mental illness Psilocybin is a prodrug which is quickly converted by the body to psilocin 4-OH-dimethyltryptamine a 5-HT2A receptor partial agonist Both psilocybin and psilocin which have psychoactive properties are naturally occurring in Psilocybe mushrooms and are structurally similar to the endogenous neurotransmitter serotonin
As a direct 5-HT2A agonist psilocybin has a unique therapeutic potential compared with other pharmacological treatment for OCD such as SSRIs Animal studies have shown increased cognitive flexibility associative learning cortical plasticity and anti-depressive effects in response to 5-HT2A activation
The first current clinical research with psilocybin examined the safety and efficacy of psilocybin in the treatment of psychological distress in patients with terminal advanced-stage cancer The double-blind placebo-controlled research was conducted in the Los Angeles Biomedical Research Institute Harbor-UCLA Medical Center Torrance California Researchers concluded that psilocybin is safe and well tolerated at 02 mgkg dose
Following this research two different research groups in Johns Hopkins University and in New York University have received FDA approval to administrate a higher dose of psilocybin in a similar clinical population These trails have shown promising results for safety psychological distress reduction and significant improvement in anxiety and depression
In their research Griffiths and colleagues examined the efficacy of psilocybin in reducing anxiety and depression in 51 patients suffering from a terminal end-stage cancer and experiencing symptoms of anxiety and depression This randomized double-blind cross-over trial investigated the effects of a very low placebo-like dose 1 or 3 mg70 kg vs a high dose 22 or 30 mg70 kg of psilocybin No serious adverse events attributed to psilocybin administration occurred There were transient moderate increases in systolic andor diastolic blood pressure after psilocybin in 34 of participants in the high-dose session and 17 of participants in the low-dose session none of these episodes met criteria for medical intervention Nausea or vomiting occurred in 15 of participants in the high-dose session An episode of physical discomfort any type occurred in 21 of participants in the high-dose session and 8 in the low-dose session Psychological discomfort any type occurred in 32 of participants in the high-dose session and 12 in the low-dose session An episode of anxiety occurred in 26 of participants in the high-dose session and 15 in the low-dose session One participant had a transient episode of paranoid ideation 2 of high-dose sessions There were no cases of hallucinogen persisting perception disorder HPPD or prolonged psychosis Across the two dose sequence groups the overall rate of clinical response at 6 months was 78 and 83 for depression and anxiety respectively and the overall rate of symptom remission at 6 months for all participants was 65 and 57 respectively
Ross and colleagues conducted a double-blind placebo-controlled crossover trial with 29 patients with cancer-related anxiety and depression that were randomly assigned and received treatment with single-dose psilocybin 03 mgkg or niacin active placebo both in conjunction with psychotherapy before and after drug administration The most common adverse effects were non-clinically significant elevations in blood pressure and heart rate 76 headachesmigraines 28 nausea 14 transient anxiety 17 and transient psychotic-like symptoms 7 The medical and psychiatric adverse effects attributable to psilocybin are all known were transient and tolerable There were no cases of prolonged psychosis or HPPD and no participants required psychiatric hospitalization Psilocybin produced immediate substantial and sustained improvements in anxiety and depression this effect was sustained at 65 months follow-up
These trails and others have shown safety of treatment and high efficacy in reduction of anxiety and depression symptoms with sustained effect at 6 months follow up These findings taken together with the theoretical understanding of psilocybin mechanism of action and with the understanding of the neuro-psychological pathology of OCD encourage investigating the potential of psilocybin as a novel significant treatment for this disorder Research of beneficial effects of psilocybin for patients with OCD is in its infancy but preliminary findings show potential efficacy in treatment of the disorder
Matsushima and colleagues used a mice model for OCD and found that psilocybin both syntactic and in mushroom form significantly inhibited compulsive behaviour marble burying without affecting locomotor activity In addition several case reports showed beneficial effects of psilocybin for people with OCD For example Leonard and Rapoport 1987 and Moreno and Delgado 1997 reported that among drug-users with OCD there was a worsening of symptoms under the influence of cocaine but a remission of symptoms for hours days following psilocybin use Wilcox 2014 described a case in which a patient with OCD self-medicated with psilocybin once every three weeks experienced a preserved effect of reduced anxiety obsessive thoughts and compulsive behaviour In another case report a patient suffering from a body dysmorphic disorder spending about 4 hours a day examining himself in the mirror has experienced a significant reduction in distress and a notable change in body perception following multiple dosing of psilocybin
Moreno et al 2006 conducted a semi open-label trial examining the effect of psilocybin on nine participants with mild to severe OCD which had at least one treatment failure defined as a lack of significant improvement after an adequate treatment Doses were 25 very low dose VLD 100 low dose LD 200 medium dose MD and 300 high dose HD µgkg LD MD and HD were assigned in that order and VLD was inserted randomly and in a double-blind fashion at any time after the first dose LD In measurements during the 24 hours after each dose all participants have experienced a significant relief in symptoms 23-100 as measured by the Yale-Brown Obsessive-Compulsive Scale YBOCS in at least one of the sessions Two of the subjects reported that their symptomatic improvement lasted most of the following week after testing One subject achieved long-term remission at the end of the 4 test sessions as measured at 6-month follow-up There was however no clear dose-response relationship to the change in YBOCS score and no correlation between YBOCS score reduction and the perceived intensity of the psychedelic experience
These preliminary findings stress the need for further research to examine the efficacy of psilocybin in the treatment of OCD In addition the only clinical trial to date did not include psychotherapy for patients while under the influence of psilocybin Earlier studies have shown that a preliminary therapeutic relationship before psilocybin administration increases the probability for a peak experience during sessions Furthermore two more recent studies have emphasized the importance of psychotherapy during and before psilocybin sessions touching on intent and formulating an early and strong therapeutic relationship There is also a reference to the psychedelic afterglow an effect lasting for days and even weeks after a psychedelic session during which there is a unique window for a meaningful transformative psychotherapeutic intervention most likely owing to the increased psychological plasticity following a psychedelic experience
The current study has two main goals 1 Determine the safety and efficacy of psilocybin for patients suffering from OCD 2 Elucidate the psychological mechanisms contributing to the beneficial effect of psilocybin on OCD symptoms
Research Plan
The current research aims to examine the feasibility safety and efficacy of psychotherapy assisted psilocybin for treatment of severe OCD The protocol includes 15 therapeutic sessions of which 12 are one-hour sessions and three are eight hours experiential sessions session 4812 under the influence of psilocybin In the first experiential session participants will receive a safety dose of 10mg70kg In the second and third sessions participants will receive a therapeutic dose of 30mg70kg Three preparatory sessions will take place before the first experiential session and three integration sessions will take place after each experiential session
The research will include 15 participants and will include the following phases
Selection phase
Research team will screen participants via phone interviews Participants answering the inclusion criteria will be invited to receive and sign consent forms Research member will collect demographics and health status data and register the participants according to study protocol
Preparatory and final registration phase
It is known that SSRIs have a counter effect on psilocybin therefore to allow a full effect of psilocybin it is necessary to avoid drug interaction and discontinue previous treatment In a period of 4 weeks participants will undergo medication withdrawal under psychiatric supervision During the 4 weeks period each participant will have 2-4 sessions as needed with the research psychiatrist to supervise their clinical state At the end of 4 weeks a psychiatric evaluation will take place to determine readiness to begin psilocybin treatment
Baseline assessment and preparatory therapeutic sessions phase
During the 5-6 weeks from registration participants will have three preparatory psychotherapy sessions with a couple of therapists assigned to their treatment Prior to their first psychotherapy session participants will complete the first-baseline assessment of research questionnaires
Treatment phase
The treatment phase includes three experiential sessions with psilocybin sessions 4 8 12 and three integration sessions after each experiential session During this phase participants will complete three assessments using research questionnaires sessions 2 10 15
End of treatment and follow-up phase
Primary outcome assessment will take place at the end of the last therapeutic session no15 Additional assessments will take place at three months and six monthsone-year follow-up
Research procedure Participants will sign consent forms before participating in the research treatment
The treatment is based on 15 therapy sessions
Three preliminary sessions for establishing therapeutic alliance with the therapists and preparing the participant for the first experiential session
An 8-hour experiential session with a safety dose of psilocybin 10mg70 kg V4
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V5
Two integration sessions and preparation for the next experiential session V6 V7
An 8-hour experiential session with a therapeutic dose of psilocybin 30mg70 kg V8
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V9
Two integration sessions and preparation for the next experiential session V10 V11
An 8-hour experiential session with a therapeutic dose of psilocybin 30mg70 kg V12
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V13
Two integration and summary sessions V14 V15
Possible discomfort
It is possible that psilocybin and the experience it induces will cause some emotional or physical discomfort Investigators will address all possible discomforts and appropriate measures to contain them in the research safety instructions
Research purpose
The main objective of this research is to use standardized measuring tools to explore the safety and efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms A secondary aim is to explore possible variables underlying change in symptoms
Research objectives
The main objective is to assess efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms This assessment will be based on comparing ratings of the main outcome measure Y-BOCS at baseline session 2 at the middle and at end of treatment session 10 15 respectively A score under 14 or a reduction of 35 in the overall score will be considered as remission Lewin Nadai Park Goodman Murphy Stroch 2011
Secondary objectives assessing safety by collecting data on side effects and assessing possible spiritual variables underlying change in symptoms via standardized questionnaires and semi constructed interviews
Safety
The general safety goal is to assess occurrence and frequency of adverse events during treatment This includes suicide ideation andor behaviour and adverse physiological or psychological responses The safety of psilocybin use was previously proven in several clinical research
Potential adverse effects
In general psychedelic drugs have low levels of physiological toxicity and previous research indicate no evidence of toxicity organ damage or neurophysiological disfunctions Possible physiological effects experienced under the influence of psychedelic substances may include dizziness weakness tremor paresthesia nausea thirst blurred vision dilated pupils and hyperreflexia These somatic effects are dynamic and relatively minor even when the psychological effect sensory perceptual and cognitive is strongintense The significant risk associated with psilocybin intake is a subjective experience of fear and anxiety panic dysphoria andor paranoia
Recent clinical studies report a high safety level with no adverse effects The high safety levels can be attributed to several control parameters described below and to complying with safety guidelines in clinical psychotherapy with psychedelics The use of psilocybin requires a significant psychotherapeutic holding of the subjective experience that will provide a safe and supportive environment during the psychedelic experience The safety guidelines in clinical psychotherapy with psychedelics describe the therapeutic presence and processes as well as the set and settings needed to provide a supportive emotional and external environment
Safety measures
1 Controlling the quality of psilocybin and ensuring it is manufactured under GMP conditions
2 Controlling for appropriate and adjusted dosage
3 Controlling a strict protocol for screening eligible participants to the study for details see inclusion-exclusion criteria section
4 Recruiting professional and experienced psychotherapists with the appropriate training for clinical psychotherapy with psychedelics Professionals will undergo a unique training to work with the psychotherapy protocol written for the current research
5 Psychotherapists will work in pairs a man and a woman to provide an optimal holding space for each participant
6 A proximity of a medical team for case of emergency
7 Providing preparatory and integration sessions before and after the psilocybin sessions
8 Preparing and using a comfortable and friendly room for the therapeutic session The physical environment in which the treatment takes place should be suitable to the physical as well as the emotional safety of the participant This means creating a lenient environment which provides a pleasant and welcoming atmosphere and may elicit a sense of intimacy and connection As opposed to the environment of a hospital a space like this supports and strengthens the participants sense of safety and connectedness thus helping himher contain the intense psychedelic experience
9 Guidelines for psychotherapy process these guidelines are based on the humanistic perspective and concern the characteristic of the therapeutic process
A supportive accepting and non-judgmental presence of the therapist
The importance of the therapeutic alliance and trust between participant and therapists
A non-directive approach supportive and gentle presence that stays with the participants unfolding experience
Viewing the mind as multi-dimensional making space for the diverse dimensions of the internal experience physical emotional and spiritual
10 Maintaining a well-documented monitoring of the study and the participants status during the study period
11 Monitoring physiological measure blood pressure heart rate and body temperature during the psychedelic sessions with psilocybin before taking the drug an hour and a half after taking the drug and 8 hours after In case of anomalies physiological measures will be monitor more frequently
12 Consulting and collaborating with other research teams with similar research interests in NYU and Imperial College in London UK
Obsessive-compulsive disorder OCD is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety accompanied by repetitive behaviours or mental rituals performed to control or alleviate this anxiety Individuals with OCD often have diminished quality of life functional impairment and cause substantial caregiver burden and personal and societal economic costs Lifetime prevalence of OCD ranges between 19-25 with patients often not responding to the offered pharmacological or psychological treatment and in extreme cases may even undergo neurosurgical interventions
There are several possible physiological mechanisms leading to the development of OCD which may indicate several possible effective treatment options Nowadays there is a consensus that the dopaminergic and serotonergic pathways are central to the development of the disorder with the basal ganglia as the main area of its origin Other brain areas involved in OCD are the orbitofrontal cortex and anterior cingulate cortex which are connected to the basal ganglia and are involved in regulating attention and awareness Abnormal activity between these areas and other subcortical areas might explain why normally unconscious information processing becomes consciousness and requires additional resources for its regulation It has also been suggested that the aversive emotional activity anxiety fear disgust experienced in OCD relates to hyperactivity in the amygdala The momentary relief brought on by the compulsive behaviour forms a positive feedback which perpetuate the disorder
The gold standard of care for OCD today is a combination of selective serotonin reuptake inhibitors SSRIs and cognitive behavioural therapy CBT Most patients will experience at least some symptomatic relief with these interventions however relapse of symptoms occur in 40-60 of patients and around 25 of patients are unresponsive to treatment Other existing treatments either pharmacological or neurosurgical possess a higher risk for serious side effects It is important to note that even for those patients who are responsive to treatment there are still significant residual impairing symptoms It thus seems that there is a real and immediate need to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients with lower risk and fewer side effects
A new and promising prospect of treatment in mental health is the use of psychedelic substances which interact with the serotonergic pathways and induce a powerful subjective experience with the potential for psychological transformation Specifically psilocybin has received attention in research as a promising alternative in the treatment of severe mental illness Psilocybin is a prodrug which is quickly converted by the body to psilocin 4-OH-dimethyltryptamine a 5-HT2A receptor partial agonist Both psilocybin and psilocin which have psychoactive properties are naturally occurring in Psilocybe mushrooms and are structurally similar to the endogenous neurotransmitter serotonin
As a direct 5-HT2A agonist psilocybin has a unique therapeutic potential compared with other pharmacological treatment for OCD such as SSRIs Animal studies have shown increased cognitive flexibility associative learning cortical plasticity and anti-depressive effects in response to 5-HT2A activation
The first current clinical research with psilocybin examined the safety and efficacy of psilocybin in the treatment of psychological distress in patients with terminal advanced-stage cancer The double-blind placebo-controlled research was conducted in the Los Angeles Biomedical Research Institute Harbor-UCLA Medical Center Torrance California Researchers concluded that psilocybin is safe and well tolerated at 02 mgkg dose
Following this research two different research groups in Johns Hopkins University and in New York University have received FDA approval to administrate a higher dose of psilocybin in a similar clinical population These trails have shown promising results for safety psychological distress reduction and significant improvement in anxiety and depression
In their research Griffiths and colleagues examined the efficacy of psilocybin in reducing anxiety and depression in 51 patients suffering from a terminal end-stage cancer and experiencing symptoms of anxiety and depression This randomized double-blind cross-over trial investigated the effects of a very low placebo-like dose 1 or 3 mg70 kg vs a high dose 22 or 30 mg70 kg of psilocybin No serious adverse events attributed to psilocybin administration occurred There were transient moderate increases in systolic andor diastolic blood pressure after psilocybin in 34 of participants in the high-dose session and 17 of participants in the low-dose session none of these episodes met criteria for medical intervention Nausea or vomiting occurred in 15 of participants in the high-dose session An episode of physical discomfort any type occurred in 21 of participants in the high-dose session and 8 in the low-dose session Psychological discomfort any type occurred in 32 of participants in the high-dose session and 12 in the low-dose session An episode of anxiety occurred in 26 of participants in the high-dose session and 15 in the low-dose session One participant had a transient episode of paranoid ideation 2 of high-dose sessions There were no cases of hallucinogen persisting perception disorder HPPD or prolonged psychosis Across the two dose sequence groups the overall rate of clinical response at 6 months was 78 and 83 for depression and anxiety respectively and the overall rate of symptom remission at 6 months for all participants was 65 and 57 respectively
Ross and colleagues conducted a double-blind placebo-controlled crossover trial with 29 patients with cancer-related anxiety and depression that were randomly assigned and received treatment with single-dose psilocybin 03 mgkg or niacin active placebo both in conjunction with psychotherapy before and after drug administration The most common adverse effects were non-clinically significant elevations in blood pressure and heart rate 76 headachesmigraines 28 nausea 14 transient anxiety 17 and transient psychotic-like symptoms 7 The medical and psychiatric adverse effects attributable to psilocybin are all known were transient and tolerable There were no cases of prolonged psychosis or HPPD and no participants required psychiatric hospitalization Psilocybin produced immediate substantial and sustained improvements in anxiety and depression this effect was sustained at 65 months follow-up
These trails and others have shown safety of treatment and high efficacy in reduction of anxiety and depression symptoms with sustained effect at 6 months follow up These findings taken together with the theoretical understanding of psilocybin mechanism of action and with the understanding of the neuro-psychological pathology of OCD encourage investigating the potential of psilocybin as a novel significant treatment for this disorder Research of beneficial effects of psilocybin for patients with OCD is in its infancy but preliminary findings show potential efficacy in treatment of the disorder
Matsushima and colleagues used a mice model for OCD and found that psilocybin both syntactic and in mushroom form significantly inhibited compulsive behaviour marble burying without affecting locomotor activity In addition several case reports showed beneficial effects of psilocybin for people with OCD For example Leonard and Rapoport 1987 and Moreno and Delgado 1997 reported that among drug-users with OCD there was a worsening of symptoms under the influence of cocaine but a remission of symptoms for hours days following psilocybin use Wilcox 2014 described a case in which a patient with OCD self-medicated with psilocybin once every three weeks experienced a preserved effect of reduced anxiety obsessive thoughts and compulsive behaviour In another case report a patient suffering from a body dysmorphic disorder spending about 4 hours a day examining himself in the mirror has experienced a significant reduction in distress and a notable change in body perception following multiple dosing of psilocybin
Moreno et al 2006 conducted a semi open-label trial examining the effect of psilocybin on nine participants with mild to severe OCD which had at least one treatment failure defined as a lack of significant improvement after an adequate treatment Doses were 25 very low dose VLD 100 low dose LD 200 medium dose MD and 300 high dose HD µgkg LD MD and HD were assigned in that order and VLD was inserted randomly and in a double-blind fashion at any time after the first dose LD In measurements during the 24 hours after each dose all participants have experienced a significant relief in symptoms 23-100 as measured by the Yale-Brown Obsessive-Compulsive Scale YBOCS in at least one of the sessions Two of the subjects reported that their symptomatic improvement lasted most of the following week after testing One subject achieved long-term remission at the end of the 4 test sessions as measured at 6-month follow-up There was however no clear dose-response relationship to the change in YBOCS score and no correlation between YBOCS score reduction and the perceived intensity of the psychedelic experience
These preliminary findings stress the need for further research to examine the efficacy of psilocybin in the treatment of OCD In addition the only clinical trial to date did not include psychotherapy for patients while under the influence of psilocybin Earlier studies have shown that a preliminary therapeutic relationship before psilocybin administration increases the probability for a peak experience during sessions Furthermore two more recent studies have emphasized the importance of psychotherapy during and before psilocybin sessions touching on intent and formulating an early and strong therapeutic relationship There is also a reference to the psychedelic afterglow an effect lasting for days and even weeks after a psychedelic session during which there is a unique window for a meaningful transformative psychotherapeutic intervention most likely owing to the increased psychological plasticity following a psychedelic experience
The current study has two main goals 1 Determine the safety and efficacy of psilocybin for patients suffering from OCD 2 Elucidate the psychological mechanisms contributing to the beneficial effect of psilocybin on OCD symptoms
Research Plan
The current research aims to examine the feasibility safety and efficacy of psychotherapy assisted psilocybin for treatment of severe OCD The protocol includes 15 therapeutic sessions of which 12 are one-hour sessions and three are eight hours experiential sessions session 4812 under the influence of psilocybin In the first experiential session participants will receive a safety dose of 10mg70kg In the second and third sessions participants will receive a therapeutic dose of 30mg70kg Three preparatory sessions will take place before the first experiential session and three integration sessions will take place after each experiential session
The research will include 15 participants and will include the following phases
Selection phase
Research team will screen participants via phone interviews Participants answering the inclusion criteria will be invited to receive and sign consent forms Research member will collect demographics and health status data and register the participants according to study protocol
Preparatory and final registration phase
It is known that SSRIs have a counter effect on psilocybin therefore to allow a full effect of psilocybin it is necessary to avoid drug interaction and discontinue previous treatment In a period of 4 weeks participants will undergo medication withdrawal under psychiatric supervision During the 4 weeks period each participant will have 2-4 sessions as needed with the research psychiatrist to supervise their clinical state At the end of 4 weeks a psychiatric evaluation will take place to determine readiness to begin psilocybin treatment
Baseline assessment and preparatory therapeutic sessions phase
During the 5-6 weeks from registration participants will have three preparatory psychotherapy sessions with a couple of therapists assigned to their treatment Prior to their first psychotherapy session participants will complete the first-baseline assessment of research questionnaires
Treatment phase
The treatment phase includes three experiential sessions with psilocybin sessions 4 8 12 and three integration sessions after each experiential session During this phase participants will complete three assessments using research questionnaires sessions 2 10 15
End of treatment and follow-up phase
Primary outcome assessment will take place at the end of the last therapeutic session no15 Additional assessments will take place at three months and six monthsone-year follow-up
Research procedure Participants will sign consent forms before participating in the research treatment
The treatment is based on 15 therapy sessions
Three preliminary sessions for establishing therapeutic alliance with the therapists and preparing the participant for the first experiential session
An 8-hour experiential session with a safety dose of psilocybin 10mg70 kg V4
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V5
Two integration sessions and preparation for the next experiential session V6 V7
An 8-hour experiential session with a therapeutic dose of psilocybin 30mg70 kg V8
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V9
Two integration sessions and preparation for the next experiential session V10 V11
An 8-hour experiential session with a therapeutic dose of psilocybin 30mg70 kg V12
Participant will spend the night at the medical facility under the supervision of a research member
A 1-hour session with the therapists on the following morning V13
Two integration and summary sessions V14 V15
Possible discomfort
It is possible that psilocybin and the experience it induces will cause some emotional or physical discomfort Investigators will address all possible discomforts and appropriate measures to contain them in the research safety instructions
Research purpose
The main objective of this research is to use standardized measuring tools to explore the safety and efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms A secondary aim is to explore possible variables underlying change in symptoms
Research objectives
The main objective is to assess efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms This assessment will be based on comparing ratings of the main outcome measure Y-BOCS at baseline session 2 at the middle and at end of treatment session 10 15 respectively A score under 14 or a reduction of 35 in the overall score will be considered as remission Lewin Nadai Park Goodman Murphy Stroch 2011
Secondary objectives assessing safety by collecting data on side effects and assessing possible spiritual variables underlying change in symptoms via standardized questionnaires and semi constructed interviews
Safety
The general safety goal is to assess occurrence and frequency of adverse events during treatment This includes suicide ideation andor behaviour and adverse physiological or psychological responses The safety of psilocybin use was previously proven in several clinical research
Potential adverse effects
In general psychedelic drugs have low levels of physiological toxicity and previous research indicate no evidence of toxicity organ damage or neurophysiological disfunctions Possible physiological effects experienced under the influence of psychedelic substances may include dizziness weakness tremor paresthesia nausea thirst blurred vision dilated pupils and hyperreflexia These somatic effects are dynamic and relatively minor even when the psychological effect sensory perceptual and cognitive is strongintense The significant risk associated with psilocybin intake is a subjective experience of fear and anxiety panic dysphoria andor paranoia
Recent clinical studies report a high safety level with no adverse effects The high safety levels can be attributed to several control parameters described below and to complying with safety guidelines in clinical psychotherapy with psychedelics The use of psilocybin requires a significant psychotherapeutic holding of the subjective experience that will provide a safe and supportive environment during the psychedelic experience The safety guidelines in clinical psychotherapy with psychedelics describe the therapeutic presence and processes as well as the set and settings needed to provide a supportive emotional and external environment
Safety measures
1 Controlling the quality of psilocybin and ensuring it is manufactured under GMP conditions
2 Controlling for appropriate and adjusted dosage
3 Controlling a strict protocol for screening eligible participants to the study for details see inclusion-exclusion criteria section
4 Recruiting professional and experienced psychotherapists with the appropriate training for clinical psychotherapy with psychedelics Professionals will undergo a unique training to work with the psychotherapy protocol written for the current research
5 Psychotherapists will work in pairs a man and a woman to provide an optimal holding space for each participant
6 A proximity of a medical team for case of emergency
7 Providing preparatory and integration sessions before and after the psilocybin sessions
8 Preparing and using a comfortable and friendly room for the therapeutic session The physical environment in which the treatment takes place should be suitable to the physical as well as the emotional safety of the participant This means creating a lenient environment which provides a pleasant and welcoming atmosphere and may elicit a sense of intimacy and connection As opposed to the environment of a hospital a space like this supports and strengthens the participants sense of safety and connectedness thus helping himher contain the intense psychedelic experience
9 Guidelines for psychotherapy process these guidelines are based on the humanistic perspective and concern the characteristic of the therapeutic process
A supportive accepting and non-judgmental presence of the therapist
The importance of the therapeutic alliance and trust between participant and therapists
A non-directive approach supportive and gentle presence that stays with the participants unfolding experience
Viewing the mind as multi-dimensional making space for the diverse dimensions of the internal experience physical emotional and spiritual
10 Maintaining a well-documented monitoring of the study and the participants status during the study period
11 Monitoring physiological measure blood pressure heart rate and body temperature during the psychedelic sessions with psilocybin before taking the drug an hour and a half after taking the drug and 8 hours after In case of anomalies physiological measures will be monitor more frequently
12 Consulting and collaborating with other research teams with similar research interests in NYU and Imperial College in London UK
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None