Cbd oil for pain food and drug administration fda

FDA and Cannabis: Research and Drug Approval Process

The FDA understands that there is increasing interest in the potential utility of cannabis for a variety of medical conditions, as well as research on the potential adverse health effects from use of cannabis.

To date, the FDA has not approved a marketing application for cannabis for the treatment of any disease or condition. The agency has, however, approved one cannabis-derived drug product: Epidiolex (cannabidiol), and three synthetic cannabis-related drug products: Marinol (dronabinol), Syndros (dronabinol), and Cesamet (nabilone). These approved drug products are only available with a prescription from a licensed healthcare provider. Importantly, the FDA has not approved any other cannabis, cannabis-derived, or cannabidiol (CBD) products currently available on the market.

CANNABIS

  • Cannabis sativa L. is a plant that contains over 80 different naturally occurring compounds called “cannabinoids”
  • Two well-known cannabinoids:
    • Cannabidiol (CBD)
    • Tetrahydrocannabinol (THC)
    • Plants are grown to produce varying concentrations of cannabinoids – THC or CBD
    • These plant variations are called cultivars

    Cannabis-derived compounds

    • Compounds occurring naturally in the plant – like CBD and THC
    • These compounds are extracted directly from the plant
    • Can be used to manufacture drug products
    • Example: highly-purified CBD extracted from the plant

    Cannabis-related compounds

    • These synthetic compounds are created in a laboratory
    • Can be used to manufacture drug products
    • Some synthetic compounds may also occur naturally in the plant and some may not
    • Examples: synthetically-derived dronabinol (also naturally occurring) and nabilone (not naturally occurring)

    FDA has approved Epidiolex, which contains a purified form of the drug substance cannabidiol (CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. That means FDA has concluded that this particular drug product is safe and effective for its intended use.

    The agency also has approved Marinol and Syndros for therapeutic uses in the United States, including for nausea associated with cancer chemotherapy and for the treatment of anorexia associated with weight loss in AIDS patients. Marinol and Syndros include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive intoxicating component of cannabis (i.e., the component responsible for the “high” people may experience from using cannabis). Another FDA-approved drug, Cesamet, contains the active ingredient nabilone, which has a chemical structure similar to THC and is synthetically derived. Cesamet, like dronabinol-containing products, is indicated for nausea associated with cancer chemotherapy.

    FDA is aware that unapproved cannabis and/or unapproved cannabis-derived products are being used to treat a number of medical conditions including, AIDS wasting, epilepsy, neuropathic pain, spasticity associated with multiple sclerosis, and cancer and chemotherapy-induced nausea. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. However, the use of unapproved cannabis and cannabis-derived products can have unpredictable and unintended consequences, including serious safety risks. Also, there has been no FDA review of data from rigorous clinical trials to support that these unapproved products are safe and efficacious for the various therapeutic uses for which they are being used.

    FDA understands the need to develop therapies for patients with unmet medical needs, and does everything it can to facilitate this process. FDA has programs such as Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review that are designed to facilitate the development of and expedite the approval of drug products. In addition, the FDA’s expanded access (sometimes called “compassionate use”) statutory and regulatory provisions are designed to facilitate the availability of investigational products to patients with serious diseases or conditions when there is no comparable or satisfactory alternative therapy available, either because the patients have exhausted treatment with or are intolerant of approved therapies, or when the patients are not eligible for an ongoing clinical trial. Through these programs and the drug approval process, FDA supports sound, scientifically-based research into the medicinal uses of drug products containing cannabis or cannabis-derived compounds and will continue to work with companies interested in bringing safe, effective, and quality products to market.

    FDA Supports Sound Scientific Research

    The FDA has an important role to play in supporting scientific research into the medical uses of cannabis and its constituents in scientifically valid investigations as part of the agency’s drug review and approval process. As a part of this role, the FDA supports those in the medical research community who intend to study cannabis by:

    1. Providing information on the process needed to conduct clinical research using cannabis.
    2. Providing information on the specific requirements needed to develop a human drug that is derived from a plant such as cannabis. In December 2016, the FDA updated its Guidance for Industry: Botanical Drug Development, which provides sponsors with guidance on submitting investigational new drug (IND) applications for botanical drug products. The FDA also has issued “Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research, Draft Guidance for Industry.”
    3. Providing specific support for investigators interested in conducting clinical research using cannabis and its constituents as a part of the IND or investigational new animal drug (INAD) process through meetings and regular interactions throughout the drug development process.
    4. Providing general support to investigators to help them understand and follow the procedures to conduct clinical research through the FDA Center for Drug Evaluation and Research (CDER) Small Business and Industry Assistance group.

    To conduct clinical research that can lead to an approved new drug, including research using materials from plants such as cannabis, researchers need to work with the FDA and submit an IND application to CDER. The IND application process gives researchers a path to follow that includes regular interactions with the FDA to support efficient drug development while protecting the patients who are enrolled in the trials. An IND includes protocols describing proposed studies, the qualifications of the investigators who will conduct the clinical studies, and assurances of informed consent and protection of the rights, safety, and welfare of the human subjects. The FDA reviews the IND to ensure that the proposed studies, generally referred to as “clinical trials,” do not place human subjects at an unreasonable risk of harm. The FDA also requires obtaining the informed consent of trial subjects and human subject protection in the conduct of the clinical trials. For research intending to develop an animal drug product, researchers would establish an INAD file with the Center for Veterinary Medicine (CVM) to conduct their research, rather than an IND with CDER.

    FDA is committed to encouraging the development of cannabis-related drug products, including CBD. Those interested in cannabis-derived and cannabis-related drug development are encouraged to contact the relevant CDER review division and CDER’s Botanical Review Team (BRT) to answer questions related to their specific drug development program. The BRT serves as an expert resource on botanical issues and has developed the Botanical Drug Development Guidance for Industry to assist those pursuing drug development in this area. FDA encourages researchers to request a Pre-Investigational New Drug application (PIND) meeting to discuss questions related to the development of a specific cannabis-derived and cannabis-related drug product.

    Please note that certain cultivars and parts of the Cannabis sativa L. plant are controlled under the Controlled Substances Act (CSA) since 1970 under the drug class “Marihuana” (commonly referred to as “marijuana”) [21 U.S.C. 802(16)]. “Marihuana” is listed in Schedule I of the CSA due to its high potential for abuse, which is attributable in large part to the psychoactive intoxicating effects of THC, and the absence of a currently accepted medical use in the United States. From 1970 until December of 2018, the definition of “marihuana” included all types of Cannabis Sativa L., regardless of THC content. However, in December 2018, the Agriculture Improvement Act of 2018 (also known as the Farm Bill) removed hemp, a type of cannabis that is very low in THC (cannabis or cannabis derivatives containing no more than 0.3% THC on a dry weight basis), from controls under the CSA. This change in the law may result in a more streamlined process for researchers to study cannabis and its derivatives, including CBD, that fall under the definition of hemp, a result which could speed the development of new drugs containing hemp.

    Conducting clinical research using cannabis-derived substances that are considered controlled substances under the CSA often involves interactions with several federal agencies. For example:

    • Protocols to conduct research with controlled substances listed in Schedule I are required to be conducted under a site-specific DEA investigator registration. For more information, see 21 CFR 1301.18. provides research-grade marijuana for scientific study. Through registration issued by DEA, NIDA is responsible for overseeing the cultivation of marijuana for medical research and has contracted with the University of Mississippi to grow marijuana for research at a secure facility. Marijuana of varying potencies and compositions along with marijuana-derived compounds are available. DEA also may allow additional growers to register with the DEA to produce and distribute marijuana for research purposes. DEA that, as the result of a recent amendment to federal law, certain forms of cannabis no longer require DEA registration to grow or manufacture.
    • Researchers work with the FDA and submit an IND or INAD application to the appropriate CDER divisions or other center offices depending on the therapeutic indication or population. If the research is intended to support the approval of an animal drug product, an INAD file should be established with CVM. Based on the results obtained in studies conducted at the IND or INAD stage, sponsors may submit a marketing application for formal approval of the drug.

    Cannabis Study Drugs Controlled Under Schedule I of the CSA (greater than 0.3% THC on a dry weight basis)

    Step 1

    Sponsor obtains pre-IND number through CDER review division to request a pre-IND meeting. For new animal drug research, a sponsor may engage with CVM to establish an INAD file. A pre-IND meeting with CDER is optional, and an opportunity to obtain FDA guidance on sponsor research plans and required content for an IND submission.

    Step 2

    The sponsor contacts NIDA or another DEA-registered source of cannabis and/or cannabis-derived substances to obtain information on the specific cultivars available, so that all necessary chemistry, manufacturing, and controls (CMC) and botanical raw material (BRM) information can be included in the IND. Importation of products controlled under the CSA are subject to DEA authorization.

    Step 3

    The sponsor may contact DEA to discuss Schedule I drug research plans that may require DEA inspection for an investigator and study site Schedule I license.

    Step 4

    Step 4: If the selected BRM or drug substance manufacturer holds a Drug Master File (DMF), the sponsor must obtain a Letter of Authorization (LOA) to reference CMC and BRM information. Alternatively, an IND submission would need to contain all necessary CMC data characterizing their study drug and ensuring it is safe for use in humans.

    Step 5

    The sponsor sends a copy of the IND and clinical protocol, including a LOA (if applicable), to FDA.

    Step 6

    FDA reviews the submitted IND. The sponsor must wait 30 calendar days following IND submission before initiating any clinical trials, unless FDA notifies the sponsor that the trials may proceed sooner. During this time, FDA has an opportunity to review the submission for safety to assure that research subjects will not be subjected to unreasonable risk.

    Step 7

    If the IND is authorized by FDA as “safe to proceed” the sponsor may then submit their clinical protocol registration application, including referenced IND number, to DEA to obtain the protocol registration. Once this is received, the sponsor contacts NIDA or another DEA-registered source to obtain the cannabis and/or cannabis-derived substances and they can then begin the study.

    For nonclinical research, including research conducted under an INAD file submitted established with CVM, there is no requirement of prior authorization of the protocol by FDA before the investigators may proceed with a protocol registration application submitted to DEA. For these nonclinical protocols, investigators may immediately pursue investigator and study site licensure, and protocol registration with DEA, so they may then obtain their Schedule I cannabis-derived study drug from supplier.

    Cannabis Study Drugs Containing Hemp (no more than 0.3% THC on a dry weight basis)

    Step 1

    Sponsor obtains pre-IND number through CDER review division to request a pre-IND meeting. For new animal drug research, a sponsor may engage with CVM to establish an INAD file. A pre-IND meeting with CDER is optional, and an opportunity to obtain FDA guidance on sponsor research plans and required content for an IND submission.

    Step 2

    Sponsor provides all applicable chemistry, manufacturing, and controls (CMC) and botanical raw material (BRM) information in the IND for review by FDA, including hemp cultivars.

    Step 3

    If the selected hemp manufacturer holds a Drug Master File (DMF), the sponsor must obtain a Letter of Authorization (LOA) to reference CMC and BRM information. Alternatively, an IND submission would need to contain all necessary CMC data characterizing their study drug and ensuring it is safe for use in humans.

    Step 4

    The sponsor sends a copy of the IND and clinical protocol, including a LOA (if applicable), to FDA.

    Step 5

    FDA reviews the submitted IND. The sponsor must wait 30 calendar days following IND submission before initiating any clinical trials, unless FDA notifies the sponsor that the trials may proceed sooner. During this time, FDA has an opportunity to review the submission for safety to assure that research subjects will not be subjected to unreasonable risk.

    FDA’s Role in the Drug Approval Process

    The FDA’s role in the regulation of drugs, including cannabis and cannabis-derived products, also includes review of applications to market drugs to determine whether proposed drug products are safe and effective for their intended indications. The FDA’s drug approval process requires that clinical trials be designed and conducted in a way that provides the agency with the necessary scientific data upon which the FDA can make its approval decisions. Without this review, the FDA cannot determine whether a drug product is safe and effective. It also cannot ensure that a drug product meets appropriate quality standards. For certain drugs that have not been approved by the FDA, the lack of FDA approval and oversight means the safety, effectiveness, and quality of the drug – including how potent it is, how pure it is, and whether the labeling is accurate or false – may vary considerably.

    FDA warns company marketing unapproved cannabidiol products with unsubstantiated claims to treat cancer, Alzheimer’s disease, opioid withdrawal, pain and pet anxiety

    Agency is expediting work to evaluate regulatory policies related to cannabis and cannabis-derived ingredients like CBD

    Today, the U.S. Food and Drug Administration announced that it has issued a warning letter to Curaleaf Inc., of Wakefield, Massachusetts, for illegally selling unapproved products containing cannabidiol (CBD) online with unsubstantiated claims that the products treat cancer, Alzheimer’s disease, opioid withdrawal, pain and pet anxiety, among other conditions or diseases.

    “As we examine potential regulatory pathways for the lawful marketing of products containing cannabis and cannabis-derived compounds like CBD, protecting and promoting public health remains our top priority. Selling unapproved products with unsubstantiated therapeutic claims — such as claims that CBD products can treat serious diseases and conditions — can put patients and consumers at risk by leading them to put off important medical care. Additionally, there are many unanswered questions about the science, safety, effectiveness and quality of unapproved products containing CBD,” said Acting FDA Commissioner Ned Sharpless, M.D. “Today’s action demonstrates that the agency stands firm in its commitment to continue monitoring the marketplace and protecting the public health by taking action as needed against companies that deceive consumers and put them at risk by illegally selling products marketed for therapeutic uses for which they are not approved, such as those claiming to treat cancer or Alzheimer’s disease. Consumers should beware of purchasing or using any such products.”

    Given the interest in products containing cannabis or cannabis-derived compounds, and CBD in particular, the FDA has and continues to take an agency-wide, integrated, and collaborative approach to addressing the regulation of products made from CBD that fall under its jurisdiction. The agency has established a high-level internal working group to explore potential pathways for various types of CBD products to be lawfully marketed. An important component of this work is obtaining and evaluating information to address outstanding questions related to the safety of CBD products that will inform the agency’s consideration of potential regulatory frameworks for CBD while maintaining the FDA’s rigorous public health standards. As part of that work, the FDA held a public hearing in May, and opened a docket for written comments, to obtain scientific data and information about the safety, manufacturing, product quality, marketing, labeling and sale of products containing cannabis or cannabis-derived compounds.

    “We will continue to work to protect the health and safety of American consumers from products that are being marketed in violation of the law through actions like those the FDA is taking today. At the same time, we also recognize the potential opportunities and significant interest in drug and other consumer products containing CBD,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D. “We understand this is an important national issue with public health impact and of interest to American hemp farmers and many other stakeholders. The agency has a well-established pathway for drug development and drug approvals, and we remain committed to evaluating the agency’s regulatory policies related to other types of CBD products. We plan to report our progress by early this fall as we expedite our work to address the many questions about CBD. The step-wise, science-based approach we’re taking protects patients and the public health, fosters innovation for safe and appropriate products, and promotes consumer confidence.”

    As described in the warning letter issued to Curaleaf, the company used product webpages, its online store and social media websites to make unfounded claims about more than a dozen different CBD products. Examples of the unsupported and unapproved claims made by the company include:

    • “CBD has been demonstrated to have properties that counteract the growth of [and/or] spread of cancer.”
    • “CBD was effective in killing human breast cancer cells.” • “CBD has also been shown to be effective in treating Parkinson’s disease.”
    • “CBD has been linked to the effective treatment of Alzheimer’s disease ….”
    • “CBD is being adopted more and more as a natural alternative to pharmaceutical-grade treatments for depression and anxiety.”
    • “CBD can also be used in conjunction with opioid medications, and a number of studies have demonstrated that CBD can in fact reduce the severity of opioid-related withdrawal and lessen the buildup of tolerance.”
    • “CBD oil is becoming a popular, all-natural source of relief used to address the symptoms of many common conditions, such as chronic pain, anxiety … ADHD.”
    • “What are the benefits of CBD oil? …. Some of the most researched and well-supported hemp oil uses include …. Anxiety, depression, post-traumatic stress disorders, and even schizophrenia …. Chronic pain from fibromyalgia, slipped spinal discs . . . Eating disorders and addiction . . ..”
    • “[V]ets will prescribe puppy Xanax to pet owners which can help in certain instances but is not necessarily a desirable medication to give your dog continually. Whereas CBD oil is natural and offers similar results without the use of chemicals.”
    • “For dogs experiencing pain, spasms, anxiety, nausea or inflammation often associated with cancer treatments, CBD (aka cannabidiol) may be a source of much-needed relief.”

    The FDA has requested responses from Curaleaf within 15 working days stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure and injunction.

    The agency continues to be concerned at the proliferation of products asserting to contain CBD that are marketed for therapeutic or medical uses that have not been approved by the FDA. The FDA approval process ensures that drugs on the market are safe and effective for their intended therapeutic uses. CBD is marketed in a variety of product types, such as oil drops, capsules, syrups, teas and topical lotions and creams. Often such products are sold online and are therefore available throughout the country. Other than one prescription human drug product to treat rare, severe forms of epilepsy, the FDA has not approved any other CBD products, and there is very limited information for other marketed CBD products, which likely differ in composition from the FDA-approved product and have not been evaluated for potential adverse effects on the body.

    Unlike drugs approved by the FDA, the manufacturing process of these products has not been subject to FDA review as part of the drug approval process, and there has been no FDA evaluation of whether these products are effective for their intended use, what the proper dosage is, how they could interact with FDA-approved drugs, or whether they have dangerous side effects or other safety concerns. Unsubstantiated claims associated with CBD products may lead consumers to put off getting important medical care, such as proper diagnosis, treatment and supportive care. For that reason, it’s important that consumers talk to a health care professional about the best way to treat diseases or conditions with existing, approved treatment options. The FDA also cautions pet owners against the use of such products and recommends talking with a veterinarian about appropriate treatment options for pets. The agency also has not approved cannabis or cannabis-derived compounds like CBD for any use in animals and cannot ensure the safety or effectiveness of these products.

    The FDA has previously sent warning letters to other companies illegally selling CBD products that claimed to prevent, diagnose, treat, or cure serious diseases, such as cancer. Some of these products were in further violation of the Federal Food, Drug and Cosmetic Act because they were marketed as dietary supplements or because they involved the addition of CBD to food.

    The agency encourages health care professionals and consumers to report adverse reactions associated with these or similar products to the agency’s MedWatch program.

    The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

    Warning Letters and Test Results for Cannabidiol-Related Products

    Over the past several years, FDA has issued several warning letters to firms that market unapproved new drugs that allegedly contain cannabidiol (CBD). As part of these actions, FDA has tested the chemical content of cannabinoid compounds in some of the products, and many were found to not contain the levels of CBD they claimed to contain. It is important to note that these products are not approved by FDA for the diagnosis, cure, mitigation, treatment, or prevention of any disease. Consumers should beware purchasing and using any such products.