DevelRx has world-leading expertise in assessing the abuse and dependence risks of new drugs that are being developed for clinical use. Our scientists have developed and experimentally proven innovative animal models to more accurately predict abuse potential of novel CNS drugs.
In collaboration with Scitegrity, we offer robust, quantitative and reproducible chemical similarity assessments of new compounds in development to drugs and chemical space with known or likely abuse potential. This includes similarity matching by Tanimoto analysis. Read more...
Our successes include not only CNS drug-candidates but also peripherally acting agents with limited brain penetration. We design abuse testing experiments tailored to the unique pharmacological profile of each new drug, supervise the safety testing, and prepare the regulatory submission. Our seamless approach ensures consistency across non-clinical and clinical testing. This integrated approach offers efficiencies in time and development costs and maximises the opportunity for regulatory approval with the optimum product labelling.
We have advised more than 50 clients on abuse/dependence evaluations for US, European, Australian and Japanese drug registrations. Our consultants are globally-acknowledged experts on the pharmacology of drugs of abuse and our track record is exemplified by the publications and communications listed below.
8-Factor Analyses and Regulatory Affairs
Our consultants have established credentials as scientific and innovative leaders in preparing regulatory submissions to the FDA that evaluate and predict the abuse potential risks of new drugs.
- 8-factor analyses
- Briefing documents to support non-clinical abuse testing programs
- Abuse potential assessment waiver submissions. Read more...
DevelRx’s consultants have more than 30 years of regulatory experience of supporting drug registrations in the USA. Our knowledge and skill in scientific negotiations with the FDA and in preparing regulatory submissions have supported 16 successful US drug registrations.
Book Chapters
Heal DJ, Gosden J, Smith SL. A guide to the evaluation of the abuse and dependence potential of novel CNS-active drug-candidates’. In: Introduction of Safety Pharmacology. Wang J (Editor-in-Chief), Beijing, China, Sun Yat-sen University Press, 2022.
Scientific Articles
Heal DJ, Gosden J, Smith SL. A critical assessment of the abuse, dependence and associated safety risks of naturally occurring and synthetic cannabinoids. Front Psychiatry, 2024; 15:1322434. doi.org/10.3389/fpsyt.2024.1322434. Read more...
Morrison FG, Van Orden LJ, Zeitz K, Kuijer EJ, Smith SL, Heal DJ, Wallace TL. Navacaprant, a novel and selective kappa opioid receptor antagonist, has no agonist properties implicated in opioid-related abuse. Neuropharmacol, 2024; 257: 110037. doi.org/10.1016/j.neuropharm.2024.110037. Read more…
Henningfield JE, Ashworth J, Heal DJ, Smith SL. Psychedelic drug abuse potential assessment for new drug applications and controlled substance scheduling: A United States perspective. J Psychopharm, 2023; 37(1): 33-44. doi: 10.1177/02698811221140004. Read more...
Henningfield JE, Coe MA, Griffiths RR, Belouin SJ, Berger A, Coker AR, Comer SD, Heal DJ, Hendricks PS, Nichols CD, Sapienza F, Vocci FJ, Zia FZ. Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling. Neuropharmacol, 2022; 218: 109220. doi.org/10.1016/j.neuropharm.2022.109220. Read more...
Gray RA, Heal DJ, Maguire DR, Gerak LR, Javors MA, Smith S, France CP. Preclinical assessment of the abuse potential of purified botanical cannabidiol: self-administration, drug discrimination, and physical dependence. J Pharmacol Exp Ther, 2022 Jul; 382(1): 54-65. doi: 10.1124/jpet.121.000988. Epub 2022 Apr 30. Read more...
Syan C, Bowen C, Heal DJ, Froger-Colléaux C, Beardsley PM, Dedic N, Hopkins SC, Campbell U, Koblan KS. Ulotaront, a novel TAAR1 agonist with 5-HT1A agonist activity, lacks abuse liability and attenuates cocaine cue-induced relapse in rats. Drug Alcohol Depend, 2022 Feb 1; 231: 109261. doi: 10.1016/j.drugalcdep.2021.109261. Epub 2021 Dec 31. Read more...
Smith SL, Dean RL, Todtenkopf MS, Heal DJ. Investigation of the reinforcing potential of samidorphan and naltrexone by fixed and progressive ratio intravenous self-administration testing in heroin-maintained rats. J Psychopharmacol, 2019 Mar; 33(3): 383-391. doi: 10.1177/0269881118822111. Epub 2019 Jan 24. Read more...
Heal DJ, Gosden J, Smith SL. Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans. Neuropharmacol, 2018; 142: 89-115. Read more...
Calderon S, Giarola A, Heal D. Regulatory Framework and Guidance to the Evaluation of the Abuse Liability of Drugs in the United States and Europe. In: Markgraf CG, Hudzik TJ, Compton DR (Eds). Nonclinical Assessment of Abuse Potential for New Pharmaceuticals. Academic Press, pp. 245–268, 2015.
Heal DJ, Buckley NW, Gosden J, Slater N, France CP, Hackett D. A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil. Neuropharmacol, 2013; 73: 348-358. Read more...
Rowley HL, Kulkarni R, Gosden J, Brammer R, Hackett D, Heal DJ. Lisdexamfetamine and immediate-release D-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity. Neuropharmacol, 2012; 63: 1064-1074. Read more...
Freeman KB, Heal DJ, McCreary AC, Woolverton WL. Assessment of ropinirole as a reinforcer in rhesus monkeys. Drug Alcohol Depend, 2012; 125: 173-177.
Sidhpura N, Redfern P, Rowley H, Heal D, Wonnacott S. Comparison of the effects of bupropion and nicotine on locomotor activation and dopamine release in vivo. Biochem Pharmacol, 2007; 74: 1292-1298. Read more...
Posters
Heal D, Rowton S, Smith S, Gosden J, Horn K, Cebers G, Blank J. Evaluation of the abuse potential of the cholesterol-24-hydroxylase inhibitor, soticlestat, in drug-discrimination and self-administration tests. T169. College on Problems of Drug Dependence Meeting, Montreal, Canada, 15th-19th June 2024.
Rowton S, Heal D, Smith S, Gosden J, Horn K, Cebers, Blank J. Assessment of withdrawal-induced physical dependence in rats after administration of the potent cholesterol-24-hydroxylase Inhibitor, soticlestat. T171. College on Problems of Drug Dependence Meeting, Montreal, Canada, 15th-19th June 2024.
Gosden J, Smith S, Atterwill C, Heal D. Essential experimental screening to evaluate the safety of novel psychedelics. T161. College on Problems of Drug Dependence Meeting, Denver, Colorado, USA, 17th-21st June 2023. See poster...
Heal D, Gosden J, Smith S. Valid and invalid designs for conducting drug discrimination experiments in abuse potential evaluations. M169. College on Problems of Drug Dependence Meeting, Denver, Colorado, USA, 17th-21st June 2023.
Morrison F, Van Orden LJ, Zeitz K,Heal D, Smith S, Wallace TL. S102. NMRA-140, a novel and selective kappa opioid receptor antagonist: Mode of action profiling studies demonstrate no opioid agonist properties implicated in opioid-related abuse. S102. College on Problems of Drug Dependence Meeting, Denver, Colorado, USA, 17th-21st June 2023. See poster...
Synan C, Bowen C, Heal D, Froger-Colleaux C, Beardsley P, Campbell U. SEP-363856, a novel TAAR1 agonist, lacks abuse liability in preclinical models and attenuates cocaine cue-induced relapse in rats. T149. American College of Neuropsychopharmacology Virtual Meeting, 6th-9th December 2020.
Heal D, Rowley H, Smith S, Elbekai R. Evaluation of the discriminative and reinforcing potential of centanafadine and reference comparator ADHD drugs by drug-discrimination and intravenous self-administration testing in rats. W51. American College of Neuropsychopharmacology Virtual Meeting, 6th-9th December 2020.
Synan C, Bowen C, Heal DJ, Froger-Colleaux C, Beardsley PM, Campbell U, Koblan KS. Preclinical abuse liability assessment of SEP-363856, a compound with a non-D2 receptor mechanism of action. College on Problems of Drug Dependence Virtual Meeting, 22nd-24th June 2020. See poster...
Gray RA, Heal DJ, Maguire DR, Gerak LR, Javors MA, Smith SL, France CP. Investigation of the reinforcing and discriminative properties of highly purified botanical cannabidiol in rats and monkeys. M233. American College of Neuropsychopharmacology Meeting, Orlando, Florida, USA, 8th-11th December 2019. See poster...
Smith SL, Heal DJ. How reinforcing is bupropion? Comparison with methylphenidate and cocaine by intravenous self-administration in rats. 157.09. Society for Neuroscience Meeting, Chicago, Illinois, USA, 19th-23rd October 2019. See poster...
Rowley HL, Kulkarni RS, Heal DJ. Dopamine measurement by in vivo microdialysis as a rapid, early screen to detect the abuse potential of novel CNS-active drug-candidates. Safety Pharmacology Society Meeting, Barcelona, Spain, 23rd-26th September 2019.
Jagger L, Heal DJ, Cheetham SC. Ex vivo receptor binding in rats as a rapid screen for CNS penetration and occupancy of abuse-related molecular targets. Safety Pharmacology Society Meeting, Barcelona, Spain, 23rd-26th September 2019. See poster...
Heal DJ, Gosden J, Smith SL. An evidence-based evaluation of the possible influence of gender on results from abuse and dependence liability testing in rats. College on Problems of Drug Dependence Meeting, San Antonio, Texas, USA, 15th-19th June 2019.
Smith S, Hallam M, Turnbull Z, Roberson D, Painter M, Yekkirala A, Heal D. An investigation of the reinforcing potential of Blue-181 in rats trained to self-administer heroin. College on Problems of Drug Dependence Meeting, San Antonio, Texas, USA, 15th-19th June 2019. See poster...
Palandri J, Bailey C, Heal DJ, Kendall D. An investigation of the reinforcing potential of PN6047 by conditioned place preference testing in rats. College on Problems of Drug Dependence Meeting, San Antonio, Texas, USA, 15th-19th June 2019. See poster...
Heal DJ, Holland S, Gosden J, Gray RA, Smith SL. An investigation of the discriminative stimulus and reinforcing effects of cannabidiol in rats. 373.13. Society for Neuroscience Meeting, San Diego, California, USA, 3rd-7th November 2018.
Smith SL, Hallam M, Heal DJ. Determination of the relative reinforcing effect of MDMA by fixed ratio (FR) and progressive ratio (PR) intravenous self-administration testing in rats. 682.10. Society for Neuroscience Meeting, San Diego, California, USA, 3rd-7th November 2018.
Smith SL, Holland SJ, Slade J, Hallam M, Heal DJ. Progressive ratio (PR) intravenous self-administration testing in rats to assess the relative reinforcing effects of a wide range of substances of abuse. Safety Pharmacology Society Meeting, Washington, DC, USA, 30th September-3rd October 2018.
Smith S, Keogh E, Holland H, Slade J, Heal D. Investigation of the reinforcing effect of barbiturates and benzodiazepines in rats trained to self-administer heroin. British Association of Psychopharmacology Meeting, London, UK, 22nd-25th July 2018.
Goddard S, Heal DJ, Smith SL. A comparison of the physical dependence syndromes produced in rats by morphine and diazepam. College on Problems of Drug Dependence Meeting, Montreal, Canada, 17th-22nd June 2017.
Smith SL, Holland S, Gray RA, Heal DJ. An investigation of the reinforcing effects of diazepam and midazolam in rats trained to self-administer heroin. College on Problems of Drug Dependence Meeting, Montreal, Canada, 17th-22nd June 2017.
Heal DJ, Smith SL. Comparison by rat intravenous self-administration (IVSA) of the reinforcing effects of nicotine versus three C-II drugs. College on Problems of Drug Dependence Meeting, Montreal, Canada, 17th-22nd June 2017.
Heal DJ, Goddard S, Gosden J, Dykes S, Slater N, Brammer R, Spencer R, Menzaghi F. A preclinical evaluation of the potential of CR845 to induce tolerance and a syndrome of dependence on withdrawal. American College of Neuropsychopharmacology Meeting, Hollywood, Florida, USA, 6th-10th December 2015.
Heal DJ, Gosden J, Slater N, Holland S, Slade J, Menzaghi F, Spencer R, Smith S. Investigation of the discriminative and reinforcing properties of the κ opioid receptor agonist CR845 in rats. 819.04. Society for Neuroscience Meeting, San Diego, California, USA, 12th-16th November 2016.
Talks
Cross-Company Abuse Liability Council Conference, Rockville, MD, USA, 27th-28th September 2023.
Advancements and Challenges in Abuse Potential Evaluation 2023. Talk entitled "Translationally valid experimental designs to evaluate the abuse potential of psychedelic drugs" presented at a meeting organised by CCALC, with scientific support and participation by the FDA, Hilton Washington DC/Rockville Hotel and Executive Meeting Center, Rockville, MD 20852, USA.
You can download the presentation here.
Safety Pharmacology Society Virtual Meeting, 4th-8th October 2021.
Talk entitled "Psychedelics and CNS Drugs with Novel Mechanisms. Non-clinical Abuse Evaluations to Meet the Challenge". Part of the Continuing Education (CE) course "CNS Biomarkers of Mood Disorders and Drug Abuse: Where are We?" associated with the SPS Virtual Meeting, 11th October 2021.
DevelRx - Altasciences Joint Podcast, 21st September 2021.
Podcast entitled "The Next Trip - Developing the Second Generation of Psychedelics and their Analogs for Targeted Medical Use". In this podcast, experts from DevelRx and Altasciences examined the preclinical, clinical and regulatory challenges facing the development of more efficacious and safer psychedelic drugs.
College on Problems of Drug Dependence Workshop at Virtual Meeting, 21st-24th June, 2021.
Talk entitled: "Refinements and Innovations in Non-clinical Abuse Evaluations" in Workshop "Meeting the Challenge of the Psychedelics and CNS Drugs with Novel Mechanisms - Building on the Foundation of the FDA 2017 Guidance on the Assessment of Abuse Potential". 23rd June 2021.
American College of Toxicology Virtual Meeting, 12th-19th November 2020.
Talk entitled: “Understanding the Assessment of Abuse Potential: An Industry and Regulatory Perspective.” Continuing Education Course.
College on Problems of Drug Dependence Workshop at Annual Meeting, San Diego, CA, USA, 9th-14th June 2018.
Talk entitled: “An evaluation of the discriminative and reinforcing properties of cannabidiol in rats." In Workshop "Therapeutic Applications and Abuse Liability Assessment of Cannabidiol".
Pinney Associates – RenaSci Supported International Webex, 2018.
Developing Psychedelics into Medicine: Potential and Pitfalls. Talk entitled: “Developing psychedelic drugs for medical use - dealing with the regulatory challenge of non-clinical abuse and dependence assessments.”
Cross-Company Abuse Liability Council Conference, Bethesda, MD, USA,11th-12th October 2018.
Advancements and Challenges in Abuse Potential Evaluation. Talk entitled: “An evidence-based evaluation of the possible influence of gender on results from drug-discrimination, intravenous self-administration and tolerance / dependence safety pharmacology testing.”
AddRess - Center for Addiction Research & Science, 2018.
Talk entitled: “Developing psychedelic drugs for medical use – regulatory challenges.”
OTHER AREAS OF EXPERTISE:
- ADHD
- Binge-Eating Disorder
- Psychiatric and Neurological Disorders
- Obesity and Metabolic Disorders
- Psychedelics and Cannabinoids
Get in touch to find out how we can help you.