RESEARCH: CANNABINOID
FOLDING PROJECT #19010 PROFILE

This project looks at how different types of 'weed' affect the body. Scientists are comparing how two different types of cannabinoids (the stuff that makes weed work) interact with our brain cells. One type is like regular marijuana, while the other is a newer synthetic version. Understanding how these cannabinoids work can help us develop better medicines and warn about the dangers of harmful synthetic versions.

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

Receptors that bind cannabinoids and play a role in pain perception, appetite, mood, and other physiological processes.

Cannabinoid receptors are specialized proteins found throughout the body. They interact with chemicals called cannabinoids, which can be produced naturally by the body (endocannabinoids) or obtained from sources like cannabis. When activated, these receptors influence various functions, including pain sensation, appetite regulation, mood, and sleep.

Endocannabinoid Signaling System

A complex network of receptors, enzymes, and neurotransmitters that plays a crucial role in maintaining homeostasis.

The endocannabinoid system is a vital communication network within the body. It uses specialized chemicals called endocannabinoids to send signals between cells and organs. This system helps regulate numerous functions, including mood, appetite, sleep, pain perception, and immune responses.

Synthetic Cannabinoids

Man-made compounds that mimic the effects of naturally occurring cannabinoids.

Synthetic cannabinoids are artificial chemicals designed to produce similar effects to those found in cannabis. These substances often target the same receptors as natural cannabinoids but may have different potencies and side effects.

Novel Psychoactive Substance (NPS)

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

Novel psychoactive substances (NPS) are a growing concern due to their unpredictable effects and potential for harm. These substances often bypass legal restrictions by slightly altering the chemical structure of existing controlled drugs.

MDMB-Fubinaca

A synthetic cannabinoid with potent effects.

MDMB-Fubinaca is a synthetic cannabinoid known for its strong psychoactive effects. It has been associated with adverse health outcomes, including agitation, hallucinations, and seizures.

HU-210

A classical cannabinoid agonist that binds to cannabinoid receptors.

HU-210 is a synthetic cannabinoid compound with known pharmacological activity. It has been studied for its potential therapeutic applications in conditions such as chronic pain and multiple sclerosis.