Psilocybin for Chronic Lower Back Pain and Depression

Overseen By David Yaden, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: MAOIs, Antidepressants, others

Disqualifiers: Bipolar, Psychosis, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

40 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. If you are taking antidepressants other than SSRIs, SNRIs, or bupropion, you must stop them at least 14 days before the psilocybin session. You must also abstain from psychoactive drugs the day before and the day of the drug administration session.

What evidence supports the effectiveness of the drug psilocybin for treating chronic lower back pain and depression?

Research shows that psilocybin, a compound found in certain mushrooms, has been effective in treating major depressive disorder and other mental health conditions. It has also shown potential in modulating immune responses, which could help with chronic pain conditions. ^{1 2 3 4 5}

Is psilocybin generally safe for human use?

Psilocybin has been studied in small clinical trials and is generally considered safe when given to screened, prepared, and supported participants in a controlled setting. There have been no significant adverse clinical events or verifiable recorded deaths reported in these studies, although some individuals may experience challenging psychological effects. ^{6 7 8 9 10}

How is the drug Psilocybin for Chronic Lower Back Pain and Depression different from other treatments?

Psilocybin is unique because it is a psychedelic compound that may offer both pain relief and mood enhancement, potentially addressing both chronic lower back pain and depression simultaneously, unlike traditional treatments that often target only one of these conditions. ^{11 12 13 14 15}

What is the purpose of this trial?

This study seeks to provide insight on psilocybin's effects on mechanisms of chronic pain among patients with co-morbid chronic low back pain and depression (CLBP+D). Participants will receive either a single high-dose of psilocybin (25mg absolute dose) or methylphenidate (40mg absolute dose). Participants will be asked to complete assessments of pain, depressive symptoms, and more general questionnaires regarding the participants experiences during the experimental sessions and the associated enduring effects.

Research Team

David B Yaden, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for individuals who have both chronic low back pain and depression. Participants will be given either a high dose of psilocybin or methylphenidate in a controlled setting, followed by assessments to track changes in their pain and mood.

Inclusion Criteria

Have given written informed consent

Be judged by study team clinicians to be at low risk for suicidality

Be otherwise medically stable as determined by screening for medical problems

Exclusion Criteria

Pregnant or nursing women

My medication doses have been stable for the last 4 weeks.

I have Type 1 diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single high-dose of psilocybin (25mg) or methylphenidate (40mg) and complete assessments of pain, depressive symptoms, and general experiences.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments conducted up to 1-month post-drug session.

4 weeks

Multiple visits (in-person and virtual)

Ecological Momentary Assessment (EMA)

Participants complete multiple daily surveys to assess momentary affect and pain over 7-day periods at baseline, post-session, and 1-month follow-up.

Throughout study participation

Treatment Details

Interventions

• Methylphenidate
• Psilocybin

Trial Overview The study is testing the effects of a single high-dose of psilocybin (25mg) compared to methylphenidate (40mg) on chronic low back pain with co-existing depression. The focus is on how these substances affect pain mechanisms and depressive symptoms.

Participant Groups

Group I: Psilocybin Experimental Treatment 1 Intervention

This arm will receive a single, absolute dose (25 mg) of psilocybin.

Group II: Methylphenidate Active Control 1 Intervention

This arm will receive a single, absolute dose (40 mg) of methylphenidate.

Methylphenidate is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in Canada as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Approved in European Union as Methylphenidate for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Narcolepsy

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

In a phase 2 clinical trial involving 233 participants with treatment-resistant depression, a single dose of 25 mg of COMP360 (synthetic psilocybin) significantly improved depression severity, anxiety, and overall functioning compared to a 1 mg control dose.

The 10 mg dose also showed some benefits, but the 25 mg dose was more effective across all measured outcomes, highlighting the potential of psilocybin as a treatment option for individuals with severe depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life. Goodwin, GM., Aaronson, ST., Alvarez, O., et al.[2023]

Psilocybin, a compound found in 'magic mushrooms', has shown potential in recent studies for treating various mental health conditions, including obsessive-compulsive disorder, alcohol and tobacco addiction, and major depressive disorder, particularly in terminally ill cancer patients.

Despite its classification as a Schedule I drug in 1970, which halted much research, there is a renewed interest in psilocybin's therapeutic effects, highlighting its importance in both historical and contemporary neuroscience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. Geiger, HA., Wurst, MG., Daniels, RN.[2019]

The PsiDeR trial is testing the feasibility of psilocybin-assisted therapy for major depressive disorder (MDD) in 60 participants who have not responded to at least two standard treatments, focusing on recruitment and dropout rates as primary outcomes.

Participants will receive either 25 mg of psilocybin or a placebo, along with psychological therapy, with the primary measure of depression assessed at 3 weeks, indicating a structured approach to evaluate both safety and efficacy of this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. Rucker, J., Jafari, H., Mantingh, T., et al.[2022]

Psilocybin, a serotonergic psychedelic, has shown promise in treating various psychiatric disorders, including depression and substance use disorders, with 9 clinical trials conducted between 2000 and 2020.

The treatment is generally well tolerated with limited side effects, and some patients with treatment-resistant conditions have experienced significant long-term improvements after just a few sessions, indicating its potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. Breeksema, JJ., Koolen, MHB., Somers, M., et al.[2021]

Psychedelic compounds from mushrooms, such as LSD and psilocybin, show promise in treating mental health disorders like major depressive disorder and anxiety, with studies indicating rapid and long-lasting effects after micro-dosing or acute dosing.

These compounds not only have a good safety profile but also may modulate the immune system, suggesting potential applications in treating autoimmune diseases and chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain. Meade, E., Hehir, S., Rowan, N., et al.[2022]

A systematic review of 44 studies involving 598 patients found that while adverse events (AEs) from psychedelics like MDMA and psilocybin were often not systematically assessed, treatments were generally well tolerated, with common AEs including nausea, headaches, and anxiety.

One serious AE was reported during MDMA treatment, but most AEs did not require medical intervention, suggesting that while there are risks, they may be manageable and that some challenging psychological experiences could even have therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review. Breeksema, JJ., Kuin, BW., Kamphuis, J., et al.[2022]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

In a survey of 1993 individuals who experienced challenging psilocybin trips, 39% rated their experience as one of the most difficult of their lives, with 11% reporting risks of physical harm, particularly influenced by dose and lack of support.

Despite the challenges, 84% of respondents felt they benefited from the experience, suggesting that while adverse effects can occur, the overall incidence of serious psychological distress is low, especially in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Carbonaro, TM., Bradstreet, MP., Barrett, FS., et al.[2018]

Psilocybin, a naturally occurring compound from certain fungi, has shown significant clinical efficacy in reducing symptoms of depression and anxiety in multiple clinical trials, indicating its potential as a treatment for psychiatric disorders.

There have been no significant adverse clinical events or recorded deaths associated with psilocybin use, suggesting it may be a safe option; however, larger studies are needed before it can be approved for widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Psilocybin in the Treatment of Psychiatric Disorders with Attention to Relative Safety Profile: A Systematic Review. Hodge, AT., Sukpraprut-Braaten, S., Narlesky, M., et al.[2023]

A study involving 20 healthy participants found that psilocybin produced stronger subjective effects compared to dextromethorphan (DXM), particularly in areas like positive mood, visual effects, and feelings of awe, which may explain its higher rates of non-medical use.

Both drugs showed significant effects compared to placebo, but psilocybin's effects increased with higher doses, while DXM did not surpass psilocybin in any measure, indicating that psilocybin may have more reinforcing properties that encourage its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan. Carbonaro, TM., Johnson, MW., Griffiths, RR.[2023]

A study involving 80 patients (40 operated and 40 non-operated) with chronic low back pain showed that xydifonum, a bisphosphonate, can provide multiple therapeutic effects, including analgesic, muscle-relaxing, anxiolytic, and antidepressant benefits, which sets it apart from other medications with limited effects.

The study utilized various administration methods for xydifonum, including electrophoretic, oral, and topical ointment forms, combined with heparin to enhance its effects, demonstrating its versatility in treating chronic low back pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mechanisms of formation of chronic low back pain relapse and their correction in patients with dorsopathy]. Seleznev, AN., Sabilo, ES., Savin, AA., et al.[2016]

In a 12-week study involving 30 older adults, duloxetine combined with Depression and Pain Care Management (DPCM) led to a 46.7% remission rate in major depressive disorder (MDD) and a 93.3% significant pain response in chronic low back pain (CLBP).

The average time to achieve depression remission was about 7.6 weeks, while pain response was quicker at 2.8 weeks, indicating that this treatment approach effectively addresses both conditions in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study. Karp, JF., Weiner, DK., Dew, MA., et al.[2022]

Most monotherapies for chronic low back pain, such as analgesics and physiotherapy, have limited effectiveness, while multidisciplinary therapy focusing on intensive exercises shows modest improvements in physical function and pain relief.

Specific diagnostic techniques like joint blocks can identify pain sources in a significant number of patients, and treatments like radiofrequency neurotomy can effectively relieve zygapophysial joint pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of chronic low back pain. Bogduk, N.[2022]

A collaborative clinical trial is being conducted to develop a personalized medicine algorithm for treating chronic low back pain (cLBP), which affects many individuals and impacts their quality of life.

The trial will test four evidence-based treatments for cLBP: duloxetine, acceptance and commitment therapy, a classification-based exercise and manual therapy intervention, and a self-management approach, all of which have moderate to high levels of evidence supporting their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based interventions to treat chronic low back pain: treatment selection for a personalized medicine approach. Mauck, MC., Aylward, AF., Barton, CE., et al.[2022]

In a study of 575 patients with chronic low back pain, the combination of oxymorphone extended release (ER) with SSRIs or SNRIs was found to be well tolerated, with no significant difference in adverse events between those taking these antidepressants and those who were not.

While serious adverse events were more frequent during the titration phase for patients on SSRIs/SNRIs, this difference was not observed during the treatment phase, indicating that oxymorphone ER can be safely used alongside these medications without compromising pain relief efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of concomitant use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors and oxymorphone extended release. Peniston, JH., Hu, X., Potts, SL., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

DARK Classics in Chemical Neuroscience: Psilocybin. [2019]

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Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

[Treatment with psilocybin: applications for patients with psychiatric disorders]. [2021]

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Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

The Use of Psilocybin in the Treatment of Psychiatric Disorders with Attention to Relative Safety Profile: A Systematic Review. [2023]

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Subjective features of the psilocybin experience that may account for its self-administration by humans: a double-blind comparison of psilocybin and dextromethorphan. [2023]

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[Mechanisms of formation of chronic low back pain relapse and their correction in patients with dorsopathy]. [2016]

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Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study. [2022]

13. Australia pubmed.ncbi.nlm.nih.gov

Management of chronic low back pain. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Evidence-based interventions to treat chronic low back pain: treatment selection for a personalized medicine approach. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Tolerability of concomitant use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors and oxymorphone extended release. [2022]