CBD Oil And Methadone


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A study suggests that CBD could help treat people with opioid addiction. But before you go buy a bottle for any use, it’s important to know that it has been FDA-approved to treat only one disease. Safety of Cannabidiol Given to Subject With Methadone or Buprenorphine The overarching goal of this study is to evaluate the potential of Cannabidiol (CBD) as an adjunctive treatment for comorbid Natural Medicines, the Authority on Integrative Medicine

CBD: The next weapon in the war against opioid addiction?

University of Florida provides funding as a founding partner of The Conversation US.

CBD, or cannabidiol, is everywhere, with word on the street saying that it can cure everything from a bad mood to cancer. However, most of these claims are not based on scientific evidence. Animal studies suggest that CBD might be beneficial for some health indications, such as pain, inflammation, arthritis and anxiety.

However, until recently, the only medical indication that CBD has been proven to treat in humans is seizures associated with pediatric epilepsy. Now, however, a recent study suggested that CBD curbed cravings in people with opioid dependence. This is one of the first double-blind controlled trials, the gold standard for drug research, to show benefit of using CBD outside epilepsy treatment. Thus, researchers can say with greater confidence that CBD may be helpful in fighting the war against opioid addiction.

While this study is very exciting, as scientists who study drugs and addiction, we want to stress that this study was very narrow and used specific, standardized amounts of CBD. Thus, the results do not suggest that buying a bottle or jar of over-the-counter CBD is going to help with opioid cravings – or any other medical conditions.

Addiction is a brain disease

In order to understand why CBD might be useful to treat opioid addiction, it is helpful to take a closer look at how addiction alters normal behavior. Addiction is broadly defined by the American Psychiatric Association as “a complex condition, a brain disease that is manifested by compulsive substance use despite harmful consequence.” Addiction is classified as a disease because addiction hijacks and alters the way how the brain processes information.

People with opioid addiction issues can often be triggered by seeing drug paraphernalia, which can trigger a relapse. Oleg Mikhaylov/Shutterstock.com

Specifically, areas of the brain critical in controlling the perception of daily and pleasurable activities are susceptible to the influence of addictive drugs. Due to the rewiring of the brain under addiction, the individual often perceives the world in context to their drug of choice. The brain learns to associate drug paraphernalia or the physical location of drug partaking in the context of receiving a drug. These cues become integral reminders and reinforcers of drug use.

These events occur with most known drugs of abuse, such as cocaine, alcohol, nicotine, methamphetamines as well as opioids.

Addiction is often thought of in terms of the pursuit of the “high” associated with the use of a drug. However, most addicts continue to use, or relapse when trying to quit using their respective addictive drug. This difficulty, despite the desire and often pressure by friends, family and co-workers to quit, is often due to the negative effects of drug withdrawal.

Depending on the drug, the symptoms of drug withdrawal can vary and range from mild to severe intensity. In the case of opioid withdrawal, symptoms often include anxiety, nausea, vomiting, diarrhea, abdominal cramps and rapid heartbeat. An individual going through opioid withdrawal experiencing extreme conditions of anxiety is likely to take opioids to alleviate that anxiety. This sort of behavior can be repetitive, leading to a what is called a feed-forward loop of dependence on an abused drug.

A person is often referred to as “dependent” on a drug when the drug must be present for the individual to function normally. Importantly, anxiety and depression are correlated with opioid dependence.

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For dependent individuals, ongoing use of a drug is not perceived as a conscious choice, but rather an evil necessity. Medication-assisted treatment with drugs like methadone or buprenorphine, allows for an individual to undergo recovery from an opioid use disorder. The use of medication assisted treatment significantly decreases the likelihood of an individual to relapse and fatally overdose due to withdrawal or dependence symptoms.

CBD and Epidiolex

CBD was tested in several clinical trials and was shown to work and to be safe in treating a rare form of epilepsy. A pharmaceutical grade CBD, Epidiolex, gained FDA approval in June 2018 for this specific usage.

CBD is currently only prescribed as the drug Epidiolex. That is because, up until now, CBD has only been shown to be safe and effective in the treatment of intractable pediatric epilepsy.

Importantly, CBD binds to different receptors than those that lead to opioid addiction.

CBD and opioid addiction

In experiments reported in 2009, rats were trained to press a lever to receive heroin. CBD did not decrease the amount of heroin that the rats self-administered, or the drug seeking behavior displayed by the rat while taking heroin. However, when rats were taken off heroin and given CBD, there was a decrease in drug-seeking behavior when the animals were exposed to a heroin-associated cue.

Initial studies of CBD in humans verified that CBD, when co-administered with fentanyl, is safe and well tolerated in healthy, non-opioid dependent individuals. A 2015 report of a small double-blind study conducted in opioid-dependent individuals found that a single administration of CBD, in comparison to a placebo, decreased cue-induced craving of opioids and feelings of anxiety. A double-blind, placebo-controlled study means that doctors and patients in the study do not know who is getting a real drug and who is getting a placebo. That is to guard against what is known as the placebo effect.

A double-blind placebo-controlled study published on May 21, 2019 adds to these findings by demonstrating that the Food and Drug Administration-approved Epidiolex can reduce cue-induced craving in individuals that had been former heroin users. Furthermore, in these individuals, Epidiolex reduced reports of anxiety, and blood levels of cortisol, a hormone known to increase under conditions of stress and anxiety.

Although further studies are needed, these studies strongly suggest that Epidiolex or CBD may hold promise as a critical weapon in fighting the opioid epidemic.

This could be a big deal.

A bottle of CBD oil may contain unpredictable amounts of CBD, and it also could contain THC. WIRACHAI/Shutterstock.com

Practical considerations

Before rushing out to purchase over-the-counter CBD to treat any medical condition, there are several practical considerations that should be considered.

Only Epidiolex is FDA-approved for a medical condition – pediatric seizures. All other forms of CBD aren’t regulated. There have been numerous consumer reports that show that the actual amount of CBD in over-the-counter products is significantly less than what is reported on the label. Also, some of these over-the-counter products contain enough THC to show up on drug tests.

Although Epidiolex was found to be safe in clinical trials, it can interact with other drugs prescribed for migraines and bipolar disorder. This could mean that taking CBD with certain drugs could diminish or enhance the effects of prescriptions, leading to problems controlling particular medical conditions that were once well-managed, or increase side effects of the other medications. For this reason, it is incredibly important to talk to your doctor or pharmacist about potential drug interactions before using CBD.

Safety of Cannabidiol Given to Subject With Methadone or Buprenorphine

The overarching goal of this study is to evaluate the potential of Cannabidiol (CBD) as an adjunctive treatment for comorbid opioid use disorder (OUD) and chronic pain. This is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of CBD on measures of pain and opioid craving in outpatients with OUD receiving medication-assisted treatment (MAT) with methadone or buprenorphine.

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Condition or disease Intervention/treatment Phase
Addiction Drug: CBD Day 1 Drug: CBD Day 2 Drug: CBD Day 3 Early Phase 1

An initial safety pilot phase will recruit six participants: three receiving treatment with methadone and three receiving treatment with buprenorphine. If the results of the pilot study support the safety of CBD administration in this clinical sample, the general study will recruit 48 participants with comorbid OUD and chronic pain, for a total of 24 completers – 12 subjects (6 men and 6 women) receiving methadone and 12 subjects (6 men and 6 women) receiving buprenorphine. Both sub-studies will enroll participants who do not currently require an inpatient hospitalization.

Layout table for study information

Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Initial safety pilot phase of 6 participants,(3 methadone and 3 on Buprenorphine) The general study is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of CBD on measures of pain and opioid craving in outpatients with OUD receiving medication-assisted treatment (MAT) with methadone or buprenorphine.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cannabidiol Pharmacotherapy for Comorbid Opioid Addiction and Chronic Pain
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : July 30, 2023
    Pain Threshold [ Time Frame: 4 measurements per test day, 3 total test days ]

The Cold Pressor (CPT measures Pain threshold (in seconds). For this test, a cooler filled with cold water (32.9-34.7degrees F/0.5-1.5 degrees C) are used. Participants are instructed to immerse their hand into the water and report the first time they experience pain (pain threshold). Lower scores indicate lower pain threshold. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

The Cold Pressor Test (CPT) measures pain threshold and pain tolerance (in seconds). For this test, a water cooler is filled with cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, Participants are then instructed to immerse their hand into the cold water bath and report when the pain becomes unbearable (pain tolerance). Lower scores indicate lower pain tolerance. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

The QST is a reliable, dynamic, and computerized method of quantifying distinct mechanisms of the pain experience

The QST is a reliable, dynamic, and computerized method of quantifying distinct mechanisms of the pain experience

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
  • Males and females, Veterans and non-Veterans, aged between 18 and 70 years old.
  • Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenance treatment.
  • Having chronic pain, uniformly operationalized as grade II (high-intensity) non- cancer pain for ≥ 6 months 49.
  • Capable of providing informed consent in English.
  • Compliant in opioid maintenance treatment and on a stable dose for four weeks or longer.
  • Not meeting DSM-5 criteria for substance use disorders other than OUD or tobacco use disorder within the last 12 months.
  • No current medical problems deemed contraindicated for participation by principal investigator.
  • For women, not pregnant as determined by pregnancy screening; not breast-feeding; using acceptable birth control methods. Acceptable contraception for females includes oral contraceptives, contraceptive depot injections, contraceptive subdermal implants, intrauterine devices, or surgical contraception methods. Acceptable contraception for males includes condoms or surgical contraception methods.
  • Other current major psychiatric disorders deemed clinically unstable by the principal investigator, such as severe depression and/or active suicidal ideation.
  • Having experienced major psychosocial stressors recently (≤ 6 weeks before enrollment), at the discretion of the principal investigator.
  • Methadone dose under 60mg or over 100mg
  • Buprenorphine over 24mg.
  • Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment).
  • Candidates receiving products containing either THC or CBD will be excluded.
  • Current use regular use other prescription opioids, gabapentinoids (pregabalin, gabapentin), antidepressants (SSRIs, SNRIs, TCAs), benzodiazepines, platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor), or NSAIDs.
  • Current weight of less of 60 kg.
  • Allergy to sesame seed oil, which is an ingredient of the CBD formulation used.
  • Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator.
  • Participants who have elevation of liver enzymes (ALT and/or AST) 2x above the normal limit or higher.
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05076370

CBD Oil And Methadone

A new report suggests that taking cannabidiol (CBD) might increase methadone levels and increase its side effects. This is especially concerning in chronic pain settings such as cancer.

A 13-year-old patient with chronic cancer pain who was previously stabilized on methadone 7.5 mg twice daily was admitted to the ER with opioid-related side effects. These side effects started 5 days prior to the ER visit, which occurred about 2 weeks after her parents increased her dose of CBD oil 4-fold. After stopping CBD, the side effects resolved. CBD may increase methadone levels by inhibiting the cytochrome P450 3A4 (CYP3A4) and CYP2C19 enzymes, which metabolize methadone. This is the first case report suggesting there is an interaction between CBD and methadone. The interaction appears to be dose-dependent – in this case, it occurred with a very high dose of CBD but not with a much lower dose. More evidence is needed to verify this interaction and to determine the CBD dose threshold at which it might occur.

Many patients and their families don’t disclose the use of natural medicines such as CBD and other cannabis products to their healthcare providers. It’s important to discuss the use of all cannabis-derived products with patients and their families. Healthcare providers should ask directly about CBD use and be aware of its potential drug interactions.

  • Does CBD Help with Chronic Pain?
  • CBD for opioid withdrawal?
  • Cannabidiol: What you need to know
  • Is CBD Safe During Pregnancy?

The information in this brief report is intended for informational purposes only, and is meant to help users better understand health concerns. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions. Copyright © 2022 Natural Medicines Inc. Commercial distribution or reproduction prohibited. Natural Medicines is the leading provider of high-quality, evidence-based, clinically-relevant information on natural medicine, dietary supplements, herbs, vitamins, minerals, functional foods, diets, complementary practices, CAM modalities, exercises and medical conditions. Monograph sections include interactions with herbs, drugs, foods and labs, contraindications, depletions, dosing, toxicology, adverse effects, pregnancy and lactation data, synonyms, safety and effectiveness.

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