Posts

NIDA Research on the Therapeutic Benefits of Cannabis and Cannabinoids

Currently there is considerable interest in the possible therapeutic uses of marijuana (see our fact sheet, “Is Marijuana Medicine?”). As of January 31, 2014, there were 28 active grants related to this topic, funded by NIDA, in 6 different disease categories (see table, below). Therapeutic research is defined here as projects that include (as at least one of their specific aims) investigation of the potential medical benefit of the marijuana plant (Cannabis sativa) or its constituentcannabinoid chemicals in human or animal models of disease.

Most of these research projects are examining the medical benefits of individual cannabinoid chemicals derived from or related to those in the marijuana plant, not the plant itself, although a few use unprocessed plant material. Individual cannabinoid chemicals may be isolated and purified from the marijuana plant or synthesized in the laboratory, or they may be naturally occurring (endogenous) cannabinoids found in the body and modified using other, non-cannabinoid chemicals.

Specifically, cannabinoids are classified here as:

  • Plant  – plant leaves, flowers, stems, and seeds collected from the Cannabis sativa plant and ingested in some form (cigarettes, vapor); also known as phytocannabinoids.
  • Endogenous – cannabinoids made by the body: N-arachidonoylethanolamine or anandamide (AE) or 2-arachidonoylglycerol ( 2-AG).  AE and 2-AG activity is manipulated by inhibiting their corresponding hydrolases FAAH or MAGL, preventing their degradation.
  • Purified – naturally occurring cannabinoids purified from plant sources:  Cannabidiol (CBD), D9-tetrahydrocannabinol (THC), and Sativex (mixture of THC and CBD).
  • Synthetic –cannabinoids synthesized in a laboratory: CB1 agonists (CPP-55, ACPA), CB2 agonists (JWH-133, NMP7, AM1241), CB1/CB2 nonselective agonist (CP55,940), Ajulemic Acid (AJA), Nabilone, Dronabinol, and several other proprietary chemicals in development as potential cannabinoid agonists and antagonists for therapeutic use.

How the Portfolio Analysis Was Conducted:

  • An internal NIH database (QVR) was searched on January 31, 2014 using the following:  TEXT word string “cannabinoid OR cannabis OR marijuana”; active grants
  • 317 grants were manually screened to identify studies in which at least one specific aim included a therapeutic focus.
  • 28 projects were identified (25 projects + 3 supplements) and are listed in the table below.

In the table, projects are divided into six disease categories:autoimmune diseases, inflammation, pain, psychiatric disorders, seizures, and substance use disorders (SUDs). Clicking on individual project titles leads to their descriptions in NIH RePorter. Also listed are the cannabinoid substances being examined and, except in cases when the whole plant was used, whether the studied chemicals are purified from the plant, synthetic, or endogenous; and whether the project uses human or animal subjects.

Autoimmune disease
Project Title Cannabinoid Study Model
TRANSDERMAL DELIVERY OF 2-ARACHIDONOYL GLYCEROL (2-AG) FOR THE TREATMENT OF ARTHR Endogenous (2-AG) Animal
Inflammation
Project Title Cannabinoid Study Model
CANNABINOID EPIGENOMIC AND MIRNA MECHANISMS IMPACT HIV/SIV DISEASE PROGRESSION Purified (THC) Animal
CANNABINOID MODULATION OF MICROGLIAL RESPONSE TO THE HIV PROTEIN TAT Purified and Synthetic (THC and CP55940) Cell culture and animal models
Pain
Project Title Cannabinoid Study Model
BEHAVIORAL ECONOMIC ANALYSIS OF MEDICAL MARIJUANA USE IN HIV+ PATIENTS Plant (cannabis cigarettes) Human
CANNABINOID MODULATION OF HYPERALGESIA Endogenous (AE and 2-AG via URB597 FAAH inhibitor and JZL184 MAGL inhibitor) Animal
CANNABINOID RECEPTOR AGONISTS FOR TREATMENT OF CHRONIC PAIN Synthetic (CB2 agonist, proprietary) Animal
OPTIMIZING ANALGESIA BY EXPLOITING CB2 AGONIST FUNCTIONAL SELECTIVITY Synthetic (CB2 agonists, proprietary) Animal
PERIPHERAL FAAH AS A TARGET FOR NOVEL ANALGESICS Endogenous (AE via FAAH inhibitor (URB937)) Animal
THE EFFECT OF VAPORIZED CANNABIS ON NEUROPATHIC PAIN IN SPINAL CORD INJURY Plant (cannabis, vaporized) Human
Psychiatric Disorder
Project Title Cannabinoid Study Model
CANNABIDIOL MODULATION OF ???-9-THC???S PSYCHOTOMIMETIC EFFECTS IN HEALTHY HUMANS Purified (Cannabidiol) Human
CANNABIS, SCHIZOPHRENIA AND REWARD: SELF-MEDICATION AND AGONIST TREATMENT? Synthetic and Plant (Dronabinol & cannabis cigarettes) Human
Seizures
Project Title Cannabinoid Study Model
NEW DRUGS TO ENHANCE ENDOCANNABINOID RESPONSES FOR TREATING EXCITOTOXICITY, PHASE Endogenous (AE via FAAH inhibitors) Animal
SUD, Withdrawal, and Dependence
Project Title Cannabinoid Study Model
CANNABINERGIC MEDICATIONS FOR METHAMPHETAMINE ADDICTION Synthetic (CB1 agonists and antagonists, proprietary) Animal
EFFICACY AND SAFETY OF DRONABINOL (ORAL THC) FOR TREATING CANNABIS DEPENDENCE Synthetic (Dronabinol) Human
EVALUATION OF NOVEL PHARMACOTHERAPIES FOR THE TREATMENT OF OPIOID DEPENDENCE Synthetic (Dronabinol, Nabilone) Human
FAAH-INHIBITOR FOR CANNABIS DEPENDENCE Endogenous (AE via PF-04457845 FAAH inhibitor) Human
MARIJUANA RELAPSE: INFLUENCE OF TOBACCO CESSATION AND VARENICLINE Sythetic (Dronabinol )+/- the noncannabinoid varenicline Human
MEDICATIONS DEVELOPMENT FOR CANNABIS-USE DISORDERS: CLINICAL STUDIES Purified (THC) and non-cannabinoids: Gabapentin & Tiagabine Human
MONOACYLGLYCEROL LIPASE INHIBITORS FOR TREATING OPIOID USE DISORDERS + supplement Endogenous (2-AG via JZL184 MAGL inhibitor) Animal
NABILONE FOR CANNABIS DEPENDENCE: IMAGING AND NEUROPSYCHOLOGICAL PERFORMANCE + supplement Synthetic (Nabilone) Human
NOVEL MEDICATION APPROACHES FOR SUBSTANCE ABUSE Synthetic (Dronabinol, Project 4)+noncannabinoid lofexidine Human
NOVEL MEDICATIONS FOR CANNABIS DEPENDENCE Synthetic (Modify THC and nabilone to create new cannabinoids) Animal
SATIVEX ASSOCIATED WITH BEHAVIOURAL-PREVENTION RELAPSE STRATEGY AS TREATMENT FOR + supplement Purified (Sativex) +/- behavioral therapy Human
STRESS-INDUCED MARIJUANA SELF-ADMINISTRATION: ROLE OF SEX AND OXYTOCIN Plant (cannabis cigarettes) Human
TREATMENT OF CANNABINOID WITHDRAWAL IN RHESUS MONKEYS Purified (THC) and Endogenous (via AEA via FAAH inhibitors) Animal