Psilocybin for Chronic Lower Back Pain and Depression

Overseen By Kelcy A Klein, BS

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how psilocybin, a compound found in certain mushrooms, might help people with ongoing lower back pain and depression. Participants will receive either psilocybin or methylphenidate (a medication often used for ADHD) to compare their effects. Individuals with chronic lower back pain for more than three months and moderate depression may be suitable for this trial. Participants will complete questionnaires about their pain and mood before and after treatment.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a single 25 mg dose of psilocybin is usually well-tolerated. In past studies, participants taking this dose often experienced a quick reduction in depression symptoms. However, some experienced side effects like worsening depression, and in rare cases, more serious issues such as psychosis (a condition where one loses touch with reality) or seizures. Importantly, no deaths by suicide were reported.

Methylphenidate, commonly used for attention deficit hyperactivity disorder (ADHD), is also known for its safety. It has been used for many years in various treatments and is generally safe when taken as directed. However, it can cause side effects like a faster heartbeat and anxiety.

In summary, research suggests that both psilocybin and methylphenidate are generally well-tolerated, though psilocybin may have some rare but serious side effects. Participants should consider these factors when deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about psilocybin for chronic lower back pain and depression because it offers a novel approach by targeting serotonin receptors in the brain, potentially altering perception and mood in a way that traditional painkillers and antidepressants do not. Unlike the usual treatments like opioids or antidepressants, which often come with significant side effects and addiction risks, psilocybin might provide relief with a single dose and minimal side effects. Meanwhile, methylphenidate, known for treating ADHD, is being explored for its potential to enhance focus and energy, which could indirectly improve mood and pain perception in these patients.

What evidence suggests that this trial's treatments could be effective for chronic lower back pain and depression?

This trial will compare the effects of psilocybin and methylphenidate on chronic lower back pain and depression. Research has shown that psilocybin might help reduce depression. In one study, a single 25 mg dose of psilocybin significantly lowered depression scores over three weeks, with participants noticing a quick drop in symptoms, even the day after taking it. Another study found that improvements in depression lasted for several weeks after just one dose.

Methylphenidate, another treatment option in this trial, is well-known for treating ADHD and is used to improve mood and focus. Its use for managing chronic pain isn't as well-established, but it might help by boosting mental clarity and energy. However, more research is needed to confirm its effectiveness specifically for chronic pain and depression. ^{1 4 5 6 7}

Who Is on the Research Team?

David B Yaden, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06355414

Psilocybin in Chronic Low Back Pain and Depression 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 ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05351541

Psilocybin Therapy for Chronic Low Back Pain This study evaluates whether psilocybin therapy helps patients cope with chronic low back pain more effectively.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206443

Single-Dose Psilocybin for a Treatment-Resistant Episode ... Psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression MADRS score change at week 3 was the primary outcome of the study though a large reduction in depressive symptoms was evident on the day following psilocybin ...

5. columbiapsychiatry.org columbiapsychiatry.org/news/psilocybin-found-rapidly-improve-depression-clinical-trial

Psilocybin Found to Rapidly Improve Depression in ... A single dose of psilocybin, combined with psychological support, generated a rapid response and significant reduction in depressive symptoms that lasted up to ...

6. journals.sagepub.com journals.sagepub.com/doi/10.1177/02698811251362390

Investigating the safety and tolerability of single-dose ... A Phase 2 trial examining single-dose COMP360 psilocybin suggested that treatment was well-tolerated, produced a rapid decrease in depressive ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12495261/

Considerations and cautions for the integration ... These adverse events included worsening depression, suicidal behaviour, psychosis, and convulsive episodes; there were no reports of death by suicide, ...