By Luke Sumpter

Since its classification as a virus in 1981, HIV has claimed over 35 million lives. This deadly disease originated in animals and spread to humans through hunting practices. Once it enters the body, the pathogen targets critical immune cells, leaving patients compromised and susceptible to everyday infections. As science continues to pitch the herb and its constituents against a wide range of health conditions, researchers are now examining if cannabis could be related to the symptoms of HIV.

What Is HIV?

HIV, or human immunodeficiency virus, is a pathogen that inflicts damage against the immune system. The cells that make up the immune system, such as white blood cells, help the body fight off infections imposed by bacteria, viruses, fungi, and other foreign organisms. Without this system, we wouldn't stay healthy for very long. These cells help to form our innate immunity (the first line of defence) and adaptive immunity (the antibody response mustered to deter specific infections). Because HIV destroys essential components of the immune system, patients are less able to fight off everyday infections and more serious pathogens.

Like all viruses, HIV works in a parasitic fashion and depends on host cells for survival. Whereas human and animal cells all contain DNA (the two-stranded molecule that contains the instructions cells need to build proteins), viruses contain RNA—a single-stranded molecule. Once viruses gain entry into host cells, they use their RNA to hijack protein-manufacturing organelles called ribosomes. In doing so, they manage to use the amino acids (the building blocks of protein) available in the cell to make more of themselves. Once the cell reaches maximum capacity, it bursts, and the newly created viruses go on to infect nearby cells. In a single day, HIV can replicate between 10 million and 10 billion times.

But HIV doesn’t just target any immune cells it comes into contact with. Instead, it targets a specific type of T-cell known as CD4 helper cells. In general, T-cells are tasked with producing antibodies[1] to fight off infections. They’re produced in the bone marrow and then sent off into systemic circulation, eventually differentiating into cell types with more specific roles in the body. During the immune response, CD4 helper cells play a critical role[2], as they produce signalling molecules designed to recruit all other types of immune system cells.

But why does HIV make an effort to target CD4 cells? It uses them as reproductive centres. The virus takes control of these cells and uses their internal machinery to reproduce. It thus reduces their lifespan[3] and overall numbers, compromising the immune system of HIV patients.

Once the virus gains a foothold, the infection unfolds in three distinct phases:

Acute phase During the weeks following infection, the virus quickly replicates and attacks CD4 cells, and patients experience flu-like symptoms.
Chronic latent phase The body develops antibodies during this time and manages to reduce viral replication. Patients often show no symptoms during this time, but CD4 cell numbers continue to wane.
Advanced infection Previously known as AIDS, this advanced stage usually develops in patients that don’t receive HIV treatment. It’s characterised by extreme damage to the immune system.
  • Where Did HIV Originate?

HIV originates from chimpanzee populations in Central Africa[4]. The virus first existed in these animals as simian immunodeficiency virus (SIV) but likely made its way into humans when natives in the area hunted chimps for bushmeat. The exact time of the first chimp to human transmission remains uncertain, but it could have occurred as far back as the 1800s.

  • Causes and Symptoms of HIV

HIV spreads from person to person through specific bodily fluids[5]. These include:

Blood Semen
Breast milk Rectal and vaginal fluids

Once a person becomes infected with HIV, they can experience a host of symptoms[6], such as:

Fatigue Sore throat
Swollen lymph nodes Mouth ulcers
Fever Chills
Rash Night sweats
Muscle aches

Understanding the Role of the Endocannabinoid System

So, where does cannabis fit into the equation? Does smoking or ingesting weed have any effect on symptoms? Unfortunately, studies remain early, so we can’t draw any conclusions. However, though limited, several cell, animal, and human studies have examined the effects of cannabis when it comes to HIV.

Before we delve into this work, it helps to gain a brief understanding of the endocannabinoid system, hereafter referred to as the ECS. To put it simply, the ECS functions as the universal regulator[7] in a host of animal species, including humans. As you’d expect from such a title, this system occurs extensively throughout the body. Researchers have located its components in neurons, bone, skin, the digestive system, the immune system, the reproductive system, and elsewhere. Ultimately, the ECS helps to maintain homeostasis (biological balance) within these systems; it keeps them working efficiently without lulling or going into overdrive. But how does it achieve this?

  • ECS Components

ECS components are present within all of the aforementioned physiological domains. The three main pieces of the ECS puzzle include receptors, signalling molecules, and enzymes. The receptors sit on the plasma membrane of different cell types (and inside cells on organelles) and await activation from signalling molecules. Two main receptors comprise the ECS, namely CB1 and CB2, but many other sites are included in the expanded ECS, known as the endocannabinoidome[8].

ECS signalling molecules are known as endocannabinoids (“endo” meaning “within”). Anandamide and 2-AG are the two primary endocannabinoids in the body. Various types of cells make and release endocannabinoids on demand; when they bind to ECS receptors, they create the desired biochemical changes within target cells.

Finally, we have the ECS enzymes. These proteins work to build endocannabinoids on demand and dismantle them shortly after they bind to receptors.

As you might already know, the cannabis plant also creates cannabinoids. These molecules (part terpene, part phenol in structure) share a similar shape to our endocannabinoids, so much so that they’re able to bind to ECS receptors. Simply put, this means molecules from cannabis have the ability to modulate the universal regulator of the human body—an impressive feat, to say the least.

Ongoing studies are now determining if this mechanism could be used to improve a long list of diseases, including HIV. For example, researchers are testing cannabinoids in models of chronic inflammation[9], neuropathic pain[10], and reduced immune system function[11].

ECS Components

Marijuana and HIV: The Research

You know about the disease process caused by HIV, and the importance of the ECS in the human body. Now it’s time to dive into some of the studies exploring the relationship of cannabis for patients with HIV.

  • Cannabis and Inflammation

Chronic inflammation underpins many diseases. The very word “inflammation” has a bad rap, but it actually helps us survive. Upon encountering an infectious pathogen, the immune system unleashes inflammatory cells and signalling molecules to launch an attack against the intruders. However, certain health conditions prevent the body from turning off this aggressive assault. In the long term, this process can start to inflict damage on bodily tissues.

While some elements of the immune system are reduced as a result of HIV infection, other components, such as monocytes, become chronically activated[12]. This can cause systemic inflammation, which places patients at a higher risk of developing cardiovascular, bone, and neurological diseases. Many HIV patients also exhibit an imbalance in their gut microbiome—the trillions of microorganisms that hold significant sway over inflammation and immunity.

Many HIV patients experience neurocognitive impairment and behavioural changes stemming from neuroinflammation caused by the virus. Several research teams have now set out to see if cannabis can play a role in dampening inflammatory signals that give rise to this symptom.

For example, a paper published in the journal AIDS Care looked at past cannabis use[13] in 138 HIV patients to see if the herb affected neurocognition. A similar study, published in the Journal of Acquired Immune Deficiency Syndromes, also looked at the impact of cannabis exposure[14] on neurocognitive impairment in 679 patients with the disease.

Additionally, a 2021 study[15] looked to determine if cannabis altered lower central nervous system inflammation in HIV patients. The researchers recruited HIV-negative patients that didn’t use cannabis, HIV-positive patients that didn’t use the herb, HIV-positive patients with a moderate pattern of use, and HIV-positive patients that used the herb every day.

  • Cannabis and Immunity

Because issues with immunity are at the core of HIV, it makes sense that researchers have sought to analyse the impact of cannabis on immunity in HIV patients. Although data from human trials remains scarce, a team of researchers proposed a study protocol in 2019 to test the effects of oral cannabinoids on immune activation in HIV patients.

The study design[16] details recruiting 26 HIV patients that have lived with undetectable viral load for at least three years. Researchers would then randomise the recruits into two groups and administer oral capsules for 12 weeks; one group would receive capsules containing a THC:CBD ratio of 1:1, and the other would receive a ratio of 1:9. The paper mentions that the Research Institute of the McGill University Health Centre approved the study. However, the results remain unpublished[17].

  • Cannabis and Pain

Hundreds of thousands of patients across the world are legally prescribed cannabis for a host of conditions, and chronic pain remains one of the most common[18]. As researchers continue to unveil the role of the ECS in pain signalling[19], studies are targeting the ECS in hopes of managing HIV-associated neuropathic pain.

On top of this, a systematic review[20] published in 2021 combed through the existing preclinical and clinical data derived from studies that pitched cannabinoids, endocannabinoids, and ECS enzyme inhibitors against models of HIV. In regard to the clinical data, most of the studies involved smoked cannabis. The authors call for future trials to explore other avenues of administration.

Marijuana and HIV: The Research
  • What Are Potential Downsides of Cannabis and HIV?

The data so far remains inconclusive on the relationship between cannabis and HIV. Moreover, cannabis has some obvious downsides that will challenge researchers and manufacturers in the coming years. While there are over 100 cannabinoids in the plant, THC and CBD are the most abundant in the majority of cultivars. THC comes with the downside of psychotropic side effects (which can exacerbate certain mental health conditions), and while CBD doesn’t cause a high, it’s known to cause an upset stomach and drowsiness in some people, and interacts with a large number of pharmaceutical drugs.

HIV and Cannabis: What Does the Future Hold?

Fortunately, support for legal cannabis continues to grow, and numerous nations already have medical cannabis programmes in place. As acceptance mounts, and data from human trials accumulates, we could reach more conclusions regarding the effects of cannabis among HIV patients.

External Resources:
  1. T cell | Definition, Function, & Facts | Britannica
  2. helper T cell | Description & Function | Britannica
  3. HIV 1: epidemiology, pathophysiology and transmission | Nursing Times
  4. About HIV/AIDS | HIV Basics | HIV/AIDS | CDC
  5. Transmission VIH / sida | Sidaction
  6. Quels sont les symptômes du VIH ? | Plate-Forme Prévention Sida
  7. The Endocannabinoid System, Our Universal Regulator
  8. The Endocannabinoid System and PPARs: Focus on Their Signalling Crosstalk, Action and Transcriptional Regulation - PMC
  9. The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease - PMC
  10. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors - PMC
  11. Cannabinoids and the immune system: an overview - PubMed
  12. Systemic Effects of Inflammation on Health during Chronic HIV Infection - PMC
  13. The neurocognitive effects of a past cannabis use disorder in a diverse sample of people living with HIV - PubMed
  14. Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV - PubMed
  15. Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV - PubMed
  16. Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028—study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation | BMJ Open
  17. Cannabinoids in PLWHIV on Effective ART - No Study Results Posted -
  18. Consensus recommendations on dosing and administration of medical cannabis to treat chronic pain: results of a modified Delphi process | Journal of Cannabis Research | Full Text
  19. The role of the endocannabinoid system in pain - PubMed
  20. Targeting the endocannabinoid system for management of HIV-associated neuropathic pain: A systematic review - PubMed
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