Cannabinoids and Sickle Cell Disease - Deciphering the Connection

Introduction

Sickle cell disease (SCD) is an uncommon blood illness. One distinctive and significant comorbidity of sickle cell disease (SCD) is pain. Vaso-occlusive crises (VOCs) are brief, erratic events that can start in infancy and last for the rest of a person's life. Furthermore, a significant percentage of SCD patients experience chronic pain, either with or without acute pain episodes. The majority of pain therapy in sickle cell disease (SCD) is opioids; however, significant dosages of opioids are necessary and can cause tolerance, pruritus, and opioid-induced hyperalgesia (OIH). To address the desire for alternate pain management therapy, cannabinoids have been extensively investigated for alleviating pain.

What Is Sickle Cell Disease?

The genetic red blood cell disease known as sickle cell disease impacts hemoglobin, the protein responsible for carrying oxygen throughout the body. Red blood cells typically have a disc shape and are sufficiently flexible to pass readily through blood arteries. A genetic abnormality causes red blood cells with sickle cell disease to take on a crescent or "sickle" form. These altered cells might obstruct blood flow to the remainder of the body because they are stiff and difficult to move. A restricted blood supply to the body can result in major issues like stroke, ocular disorders, infections, and excruciating periods of pain, known as pain crises.

The sickle cell disease is incurable. A bone marrow transplant, the only known treatment for sickle cell disease (SCD), entails significant safety hazards. Stem cell therapy, analgesics, and blood transfusions are standard treatments. Opioids like Morphine are used if overall SCD pain is more severe, but there are risks associated with these drugs, such as addiction and overdose. Scientists are, therefore, looking for more effective strategies to treat discomfort associated with SCD. There is increasing evidence that cannabis may assist SCD patients in managing their pain. Cannabis may help with symptoms but is not a cure for sickle cell disease.

What Are the Symptoms?

Since sickle cell disease is inherited, a baby is born with the disease. However, the majority of babies do not develop any disease-related issues until they are around five or six months old. Sickle cell disease symptoms might vary from person to person and may also alter over time.

Some of the early symptoms are as follows:

• When many red blood cells undergo hemolysis, the skin (jaundice) or the whites of the eyes (icterus) take on a yellowish hue.

• Severe exhaustion or irritation due to anemia (a condition in which the body can not receive adequate oxygen since there are insufficient amounts of normal red blood cells).

• Dactylitis (an enlargement of the hands and feet).

What Are Cannabinoids?

The class of molecules known as cannabinoids is vast and includes synthetic, endogenously generated, and plant-derived substances that operate through cannabinoid receptors 1 and 2, along with potentially other receptors. The two main plant-derived cannabinoids generated from Cannabis sativa L. are cannabidiol (CBD) and tetrahydrocannabinol (THC). The primary psychoactive ingredient is THC. Humans get a joyful feeling from THC.

Cannabinoids primarily affect the cannabinoid-1 (CB-1R) and cannabinoid-2 (CB-2R) receptors after they reach the body. The immune system and the central nervous system both include these receptors. Tiny proteins on cells called receptors are responsible for receiving information from factors like hormones and medications. They aid in the proper response of cells. SCD symptoms like pain and inflammation are both regulated in part by the activity of these receptors.

Pain, appetite, mental activity, reward (addiction), neuroexcitability, balance, thermoregulation, and motor function have all been demonstrated to be modulated by CB1R activation. Mainly expressed in immune cells, CB2R regulates immune cell proliferation, inflammation, pain, and immunological challenge. It has been proposed that CBD acts through CB1R regulation and possibly additional mechanisms. Additionally, THC causes a significant dopamine release in the brain. Dopamine is a pleasure chemical that is found naturally. It affects the feelings and sense of "reward." Through stimulation of the reward system in the brain, THC may lessen the sensation of pain.

What Effects Does Cannabis Have on the Pain of Sickle Cell Disease?

Through their interactions with CB1Rs and CB2Rs, cannabinoids reduce inflammation, mast cell activation, leukocyte trafficking and adhesion, oxidative stress, ischemia/reperfusion injury, and neurogenic inflammation. These all intensify pain and could be the cause of symptoms of sickle cell disease (SCD), such as retinopathy, poor wound healing, and kidney damage.

While CB1Rs are the main pathway via which THC has an anti-inflammatory impact, research suggests that CB2Rs are also important for controlling inflammation. Cannabinoids, therefore, can address a variety of processes driving pain in SCD and other illnesses.

What Kinds of Cannabis Might Be Useful in Treating Sickle Cell Disease Pain?

Medical cannabis is available for purchase in several forms, such as:

• Dried herb for smoking.

• Cartridges for electronic cigarettes.

• Edibles (candies, baked pastries, or pill capsules).

• Oils.

• Topicals.

• Patches.

• Tinctures.

A 2020 survey found that a large number of SCD patients either smoke medical marijuana or eat edibles. While eating cannabis offered longer-lasting pain alleviation, inhaled cannabis had a speedier onset. To determine whether cannabis administered in different forms, such as extracts, can also assist in relieving pain from sickle cell disease, further study is required.

What Clinical Research Have Been Conducted to Assess the Impact of Cannabis on Pain?

Clinical trials have assessed the analgesic effects of cannabis and cannabinoids in a range of illness states. Research suggests that smoked cannabis may help with analgesia in cases of continuous and neurological pain, but smoking has risks and disorders all its own. For this reason, researchers are also looking at alternative cannabis formulations and delivery methods.

Several further clinical trials with individuals with chronic pain from other diseases have been done, utilizing cannabis and THC formulations. The findings of this research suggest that there is little to no impact on the reduction of chronic pain, enhancement of sleep quality, and enhancement of quality of life. These trials have also shown a low incidence of side effects and indicate that modest dosages are tolerated effectively.

Users of cannabis reported better moods, less painkiller use, better sleep, and better symptoms of anxiety and despair. Furthermore, according to the survey, 58 percent of participants expressed interest in taking part in upcoming clinical trials investigating the use of cannabis to treat SCD pain.

Conclusion

Sickle Cell Disease (SCD) is associated with a significant number of distinct comorbidities, including both acute pain and chronic pain that can last a lifetime for an individual with the disease. The most common uses of cannabis and its derivatives are by individuals with sickle cell disease (SCD) and for pain relief under different circumstances. Cannabis products are being used for SCD more frequently due to the availability of "medical cannabis."