In 1989, Congress mandated the establishment of the Pharmacotherapies Development Program within NIDA. As a result of this mandate, in 1990 NIDA created the Medications Development Division, now the Division of Therapeutics and Medical Consequences (DTMC), to operationalize the goals of the program.
The DTMC supports and conducts studies to evaluate the safety and efficacy of pharmacotherapies, behavioral therapies, and devices to treat Substance Use Disorders (SUDs). The DTMC models aspects of a pharmaceutical company, with the resources to conduct and support all phases of medications development including synthesis and preclinical evaluation of potential therapeutics, clinical trial design and execution, and preparing regulatory submissions. The Division also supports research on behavioral therapies to treat substance use disorders as well as research on the medical consequences of drug abuse. The Division funds these efforts through peer reviewed grants, contracts, and interagency agreements. Further details on the Division’s programs are provided below:
The Pharmacotherapies Development Program integrates the expertise of multiple Branches to facilitate the advancement of novel medications (small molecules and biologics) from lead selection through clinical safety and efficacy studies in substance use disorders (SUDs). Projects focused on cocaine, methamphetamine and marijuana use disorders are a high priority for NIDA because there are currently no FDA-approved treatments for these indications. While multiple medications are available to treat opioid use disorders, the ongoing opioid overdose epidemic underscores a need for improved treatment options. Likewise, the high failure and relapse rates seen with currently available smoking cessation products argue for an expansion of treatment options. NIDA is poised to facilitate the advancement of such projects through grant and/or contract support (a detailed description of opportunities to access NIDA contract testing through the Division’s Addiction Treatment Discovery Program is provided immediately below). Moreover, DTMC staff can provide advice on all phases of development (data interpretation, regulatory requirements, study design - preclinical and clinical) at no cost to the sponsor (including academic, pharmaceutical and biotechnology organizations) to assist in advancing relevant programs. These services are provided for both NIDA funded and externally supported programs.
Program contacts: Please review the Division’s Branch listing and select the Branch that appears most appropriate for a given project’s stage of development.
Mission Statement: To identify, evaluate, and recommend potential pharmacotherapies as treatments for the medical management of substance use disorders through preclinical testing.
The ATDP accepts compounds from both academic institutions and pharmaceutical companies, evaluating these molecules in relevant preclinical models based on the indicated substance use disorder and targeted aspect of addiction. Testing is conducted under blinded conditions by contractors using NIDA-approved protocols. Individualized testing plans for submitted compounds are prepared collaboratively with the compound submitter and shaped by existing data. The ATDP evaluates compounds for effects on drug taking, relapse to drug seeking, drug withdrawal, and reward/anhedonia in established protocols to determine potential efficacy and liabilities. Compounds with completely novel mechanisms might be characterized in additional behavioral assays, including locomotor activity and drug discrimination. The ATDP also develops behavioral assays for the evaluation of a particular compound as needed. For a comprehensive list, see the table below. Compounds are accepted for evaluation based on both in vitro and in vivo data.
Efficacy Testing Conducted by the ATDP
|Drug of Abuse||Self-Administration
(Effects on Drug Taking)
(Effects on Withdrawal)
|Cocaine||Primate||Rat (prime, cue, stress)||-||Rat|
|Nicotine||Rat and primate||Rat and primate (prime and cue)||Mouse||Rat|
|Cannabinoids||Primate||Primate (prime and cue)||-||-|
|Methamphetamine||*||Rat (prime and cue)||-||Rat|
|Heroin/Opiates||*||Rat (prime and cue)||Mouse or rat||*|
*Can be developed in rodents as necessary
Note: Additional behavioral assays not listed in the table above can be developed on an as needed basis.
In addition to the testing described above, in vitro selectivity assays and predictive safety tests are available, including in silico computational toxicology, the hERG channel assay to predict QT prolongation, the Spot Ames test to predict mutagenicity, and cytochrome P450 assays to predict drug interactions. Such testing can be used to facilitate lead selection and optimization.
Compound evaluation is free of charge to submitters through NIDA contracts and interagency agreements. Test results are held confidential and forwarded to compound submitters, who retain all rights to the data.
The ATDP is interested in evaluating compounds which are selective for known targets or engage novel targets or pathways. Potential submitters are also encouraged to suggest or submit novel compounds for evaluation based on a theoretical rationale for which there are supporting preclinical data.
Program Contact: David White, Ph.D., Director, ATDP (301) 827-5981
The Regulatory Affairs Branch (RAB) serves as the Division’s primary contact to the U.S. Food and Drug Administration (FDA). In this capacity, the RAB conducts the filing of Investigational New Drug (IND) applications, Drug Master Files (DMFs) and supporting documents as new medications enter or complete clinical studies. The RAB ensures that DTMC's studies are in compliance with all applicable U.S. regulatory requirements. Consultation and advice on regulatory requirements, nonclinical and clinical medication development requirements, and strategy is provided to NIDA grantees, potential development partners, federal agencies, contractors, and other interested parties regarding projects of mutual interest.
Program Contact: Robert Walsh, Chief, Regulatory Affairs Branch, phone (301) 827-5244 and e-mail: email@example.com.
The Behavioral Therapy Development Program within the DTMC supports Stage I (treatment generation, refinement), II (efficacy) and III (efficacy in the real-world) research. Research to test efficacy, examine theory-derived targets/mechanisms of behavior change that underlie treatment, and studies that optimize combined, sequential, or integrated behavioral/pharmacological treatments are supported.
Program Contact: Will M. Aklin, Ph.D., Research Grants Branch, phone (301) 827-5909