# The Next Generation of Hallucinogens: A New Class of Synthetic Psychoactive Drugs

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $348,750

## Abstract

Project Summary
Synthetic Psychoactive Drugs (SPDs) are substances designed to mimic the effects of controlled substances
and other abused drugs. Although designer drugs are not a new phenomenon, the number and availability of
SPDs is unprecedented and has increased dramatically over the last 5 years. Many hallucinogenic SPDs are
structurally similar derivatives of known serotonergic hallucinogens, including drugs such as 25I-NBOMe (“25-
I”, “N-Bomb”), 1-propionyl-LSD, and 5-MeO-DALT. The popularity and proliferation of hallucinogenic SPDs is
causing a significant public health problem because they are often highly potent and pose greater risks of
toxicity compared with older hallucinogens. Because very little is known about the mechanisms of action and
behavioral effects of hallucinogenic SPDs, a NIDA program announcement (PAR-14-106) is soliciting research
into “Synthetic Psychoactive Drugs and Strategic Approaches to Counteract Their Deleterious Effects.” This
application seeks support for a project to investigate the specific pharmacological mechanisms, receptor
targets, and signaling pathways that mediate the behavioral effects of hallucinogenic SPDs. The proposed
research program is part of a larger collaborative effort to rapidly identify and characterize new SPDs, define
their structure-activity relationships (SAR), and determine the mechanisms of their hallucinogenic and toxic
actions. Hallucinogenic drug effects in rodents are assessed using two complementary behavioral paradigms:
exploratory locomotor behavior, which has a direct counterpart in human studies; and the head twitch response
(HTR), which is a hallucinogen-sensitive behavioral assay. Aim 1 will elucidate the mechanisms of action of
SPD analogs of indoleamine hallucinogens, testing the hypothesis that these hallucinogenic SPDs (including
tryptamines, benzofurans, and LSD analogs) act through 5-HT1A and 5-HT2A receptors. Studies will compare
SPD effects with the known profiles of serotonergic hallucinogens and define the SAR of SPD analogs of
indoleamine hallucinogens. Aim 2 will elucidate the structural features and second messenger systems
mediating the behavioral effects of the highly potent N-benzylphenethylamine class of hallucinogenic SPDs,
known as “NBOMes,” that are related to hallucinogens such as mescaline. Aim 2 studies are designed to
assess (1) the link between specific structural features in NBOMes and their 5-HT2A affinities, and (2) the
contributions of specific signaling pathways and 5-HT2A functional selectivity to the behavioral effects of these
hallucinogenic SPDs. Aim 3 will assess the contributions of metabolites to the behavioral and toxicological
effects of hallucinogenic SPDs. The idea that 1P-LSD acts as a pro-drug for LSD and the hypothesis that
some SPD toxicity is due to O-demethylated metabolites will be tested. These studies address receptor
interactions that have important implications for understanding the psychotomimetic effects of hallucinog...

## Key facts

- **NIH application ID:** 9836838
- **Project number:** 5R01DA041336-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ADAM L. Halberstadt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2017-02-15 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836838

## Citation

> US National Institutes of Health, RePORTER application 9836838, The Next Generation of Hallucinogens: A New Class of Synthetic Psychoactive Drugs (5R01DA041336-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836838. Licensed CC0.

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