Neural pathways intertwined with cannabis leaves and HIV-1 glycoproteins

CBD and HIV: What You Need to Know About Cannabinoids and Pain Management

Samir D’Costa in Health & Wellness December 2025 • 4 min read.

"Exploring the interaction between HIV-1-gp120 and cannabinoid analgesic effectiveness for better pain management strategies."

The therapeutic use of cannabinoids by HIV-1-infected individuals and the interest in the medicinal use of cannabinoids, particularly for pain management, highlights the need to understand their potential interactions with HIV-1. Research aims to determine any interactions between HIV-1 proteins and the analgesic effectiveness of cannabinoids at a supraspinal level.

A key area of focus is the periaqueductal gray (PAG), a brainstem region vital for descending pain control. The PAG modulates nociceptive neurotransmission at the spinal cord level via the rostral ventromedial medulla (RVM). This PAG-RVM pathway can either inhibit or facilitate pain, influencing how the brain perceives and responds to painful stimuli.

Studies have shown that the brain is one of the initial sites targeted by HIV-1. The virus, entering early in the disease, can lead to central nervous system (CNS) dysfunction. HIV-1 enters cells by binding its envelope glycoprotein gp120 to CD4 receptors and co-receptors. This process can trigger neurobehavioral effects characteristic of HIV-1/AIDS, leading to neurodegeneration and gliosis.

How Does HIV-1 gp120 Impact Cannabinoid Analgesia?

Neural pathways intertwined with cannabis leaves and HIV-1 glycoproteins

Research has uncovered that gp120, a key envelope glycoprotein of HIV-1, diminishes the analgesic effectiveness of cannabinoid agonists like WIN55,212-2 when introduced into the PAG. This suggests that gp120 interacts with the cannabinoid system through descending modulatory pain pathways centered in the PAG, impairing the analgesic effects of cannabinoids.

To investigate these interactions, scientists conducted experiments using animal models. Rats were pretreated with HIV-1 envelope glycoprotein 120 (gp120) in the PAG, then the effect on cannabinoid receptor agonist WIN55,212-2-induced analgesia was examined. Results indicated that gp120 in the PAG significantly reduced the analgesic effectiveness of WIN55,212-2.

Animal Models: Young adult male rats (Sprague-Dawley) were used to study the effects.
Stereotaxic Injections: HIV-1 envelope glycoprotein 120 (gp120) was introduced into the periaqueductal gray (PAG) area.
Cannabinoid Agonist: The effect of gp120 on cannabinoid receptor agonist WIN55,212-2-induced analgesia was examined.
Nociceptive Testing: A hot-plate test was used to assess pain response and analgesic effectiveness.

Researchers explored the role of CXCR4, a chemokine receptor, in mediating gp120’s effects. By administering AMD3100, a CXCR4 antagonist, they found that it could reverse the inhibitory effect of gp120 on WIN 55,212-2-induced analgesia. This suggests that the interaction between gp120 and cannabinoid analgesia involves the CXCR4 pathway in the PAG.

Future Research and Therapeutic Implications

Further research is needed to fully understand the interplay between HIV-1 components and the cannabinoid system in pain modulation. Studies should explore whether these interactions occur in HIV-1 neuropathic pain models, investigate potential sex differences, and examine the roles of gp120 and cannabinoids in other components of the descending pain modulatory system, such as the RVM. Understanding this interaction could pave the way for therapeutic strategies to improve pain management in HIV-1-infected individuals.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s00210-018-1533-1, Alternate LINK

Title: Supraspinal Interaction Between Hiv-1-Gp120 And Cannabinoid Analgesic Effectiveness

Subject: Pharmacology

Journal: Naunyn-Schmiedeberg's Archives of Pharmacology

Publisher: Springer Science and Business Media LLC

Authors: Jonathan Palma, Madhusudhanan Narasimhan, Josée Guindon, Khalid Benamar

Published: 2018-07-15

Everything You Need To Know

How does HIV-1 impact the central nervous system, and what role does gp120 play in this process?

HIV-1 targets the brain early in the disease, leading to central nervous system (CNS) dysfunction. HIV-1 enters cells by binding its envelope glycoprotein gp120 to CD4 receptors and co-receptors, triggering neurobehavioral effects characteristic of HIV-1/AIDS, including neurodegeneration and gliosis. This process contributes to the neurological complications observed in HIV-1-infected individuals.

What is the periaqueductal gray (PAG), and why is it important in the context of cannabinoid analgesia and HIV-1?

The periaqueductal gray (PAG) is a brainstem region vital for descending pain control. It modulates nociceptive neurotransmission at the spinal cord level via the rostral ventromedial medulla (RVM). This PAG-RVM pathway can either inhibit or facilitate pain, influencing how the brain perceives and responds to painful stimuli. Studies suggest HIV-1 envelope glycoprotein gp120 diminishes the analgesic effectiveness of cannabinoid agonists when introduced into the PAG.

How does HIV-1 envelope glycoprotein gp120 affect the effectiveness of cannabinoids for pain relief, and what is the role of the CXCR4 pathway in this interaction?

HIV-1 envelope glycoprotein gp120 diminishes the analgesic effectiveness of cannabinoid agonists like WIN55,212-2 when introduced into the periaqueductal gray (PAG). Research indicates that gp120 interacts with the cannabinoid system through descending modulatory pain pathways centered in the PAG, impairing the analgesic effects of cannabinoids. Administering AMD3100, a CXCR4 antagonist, can reverse the inhibitory effect of gp120 on WIN 55,212-2-induced analgesia, suggesting that the interaction between gp120 and cannabinoid analgesia involves the CXCR4 pathway in the PAG.

What future research is needed to better understand the relationship between HIV-1 and cannabinoid-based pain management?

Further research is needed to fully understand the interplay between HIV-1 components and the cannabinoid system in pain modulation. Studies should explore whether these interactions occur in HIV-1 neuropathic pain models, investigate potential sex differences, and examine the roles of gp120 and cannabinoids in other components of the descending pain modulatory system, such as the rostral ventromedial medulla (RVM). A comprehensive understanding could help improve pain management strategies for HIV-1-infected individuals.

Which cannabinoid receptor agonist was used in the animal model experiments to study the impact of HIV-1 envelope glycoprotein gp120 on pain relief, and what were the key findings?

The cannabinoid receptor agonist WIN55,212-2 was used in animal model experiments to study the impact of HIV-1 envelope glycoprotein gp120 on pain relief. The key finding was that gp120 in the periaqueductal gray (PAG) significantly reduced the analgesic effectiveness of WIN55,212-2, indicating that gp120 interacts with the cannabinoid system, impairing the analgesic effects of cannabinoids.