RESEARCH: CANNABINOID
FOLDING PROJECT #19012 PROFILE

This project compares how two types of synthetic marijuana, MDMB-Fubinaca (non-classical) and HU-210 (classical), interact with cannabinoid receptors. The goal is to understand why non-classical cannabinoids cause more harmful side effects than classical ones.

Cannabinoid Receptors Cannabinoid receptors (CBs) are part of the endocannabinoid signaling system, which help to maintain homeostasis in neuron signaling to control pain, obesity, and other neurological disorders.

Therefore, synthetic cannabinoids (SCs) were designed and tested to target CBs as potential therapeutical selective drugs.

Initially, SCs were designed by modulating the scaffolds of known phytocannabinoids.

However, chemically diverse synthetic cannabinoids (Novel Psychoactive Substance (NPS)) were
discovered rapidly, which have a high affinity towards CBs and significantly modulate the receptor activities.

These molecules were started to get sold in the market as abusive drugs under different brand names (e.g., K2, spice) and caused thousands of hospitalizations of patients across the US due to more adverse effects, including impairment of fine motor skills and increased blood pressure, tachycardia.

It is hypothesized that β-arrestin biased downstream signaling of these NPSs causes more adversarial effects compared to classical cannabinoids.

However, how these classical and non-classical cannabinoids affect receptor conformational dynamics distinctly,
has not been mechanistically studied.

In this project, we compare the unbinding mechanism and kinetics of a non-classical cannabinoid, MDMB-Fubinaca, and a classical cannabinoid, HU-210, using biased and unbiased simulation.

Cannabinoid Receptors

Proteins in the body that bind to cannabinoids.

Cannabinoid receptors are proteins found throughout the body that respond to cannabinoids like THC and CBD. They play a role in regulating various functions, including pain perception, appetite, mood, and memory.

Endocannabinoid Signaling System

A complex system of neurotransmitters and receptors that regulates various bodily functions.

The endocannabinoid system is a network of chemicals and receptors throughout the body that helps maintain balance and regulate processes like appetite, mood, sleep, and pain perception.

Synthetic Cannabinoids

Man-made substances that mimic the effects of natural cannabinoids.

Synthetic cannabinoids are artificial chemicals designed to produce similar effects to cannabis. They often have unpredictable and potentially harmful consequences due to their varying potency and unknown long-term effects.

Novel Psychoactive Substance (NPS)

New psychoactive substances are synthetic drugs designed to mimic the effects of other drugs.

NPSs are a rapidly evolving category of drugs that often bypass legal restrictions. They can produce unpredictable and dangerous effects because their chemical structures and long-term impacts are poorly understood.

MDMB-Fubinaca

A synthetic cannabinoid with high affinity for CB1 receptors.

MDMB-Fubinaca is a potent synthetic cannabinoid that has been linked to severe health problems and hospitalizations. It acts by binding to the CB1 receptor in the brain, mimicking the effects of THC.

HU-210

A classical cannabinoid with high affinity for CB1 receptors.

HU-210 is a synthetic cannabinoid that was originally developed as a research tool. It binds strongly to the CB1 receptor in the brain and is known to produce psychoactive effects.