Medical Marijuana: Marijuana-based Medicines

Despite mounting scientific evidence of marijuana’s medicinal benefits, the Drug Enforcement Agency (DEA) still maintains its status as a Schedule I drug. That means it is classified as a substance with no currently accepted medical use and has a high potential for abuse. As a result, even though some states have already legalized cannabis use, all forms of marijuana are still illegal at the federal level.

But did you know that the Food and Drug Authority (FDA) has approved several medicines containing synthetic cannabinoids or even those derived from marijuana? So, what gives?

Marijuana-based Medicines

Due to legal restrictions and its infamous reputation as an illicit drug, it is difficult to conduct studies and clinical trials using cannabis. Hence, the available research is quite scant. Despite that, the few existing research findings show marijuana’s immense potential in remedying various diseases. This piqued the clinicians’ interest and even led to the innovation of medicines using cannabinoids from marijuana as its main active ingredient such as follows:

Sativex® (Nabiximols)

Sativex is the first FDA-approved marijuana-based prescription medicine. It was launched and approved in Canada and Europe way back in 2010 under GW Pharmaceuticals Ltd. However, it is still pending regulatory approval in the U.S.

This medication contains a 1:1 ratio of delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). Specifically, each 100 microliter spray contains 2.7 mg of THC and 2.5 mg of CBD. It is used to treat and manage neuropathic pain caused by diseases like advanced cancer, multiple sclerosis, and muscle spasticity. Sativex is commonly prescribed in patients who have not responded adequately to other therapy solutions and who demonstrate significant improvement during this therapy’s initial trial.

A study evaluating Sativex’s efficacy and effectiveness in relieving pain conducted five (5) randomized controlled trials on 368 patients with various neurological conditions such as multiple sclerosis. In some tests, the Sativex spray significantly reduced neuropathic pain, spasticity, muscle spasms, and sleep disturbances.

Side Effects

The use of Sativex could cause some side effects brought on by mild THC intoxication in those with low tolerance. But unless the symptoms are severe and persistent, it should not be a cause of concern.

• Dizziness
• Drowsiness/sleepiness
• Fatigue
• Intense euphoria and feelings of intoxication
• Heightened sensory awareness
• Altered time perception
• Reddened conjunctiva
• Dry mouth
• Rapid heartbeat

If Sativex is consumed more than the prescribed dosage, it may result in moderate or even severe THC intoxication. There is a possibility that you may experience some of the following adverse effects:

• Memory impairment
• Mood alteration
• Urinary retention
• Reduced bowel motility
• Impairment of motor coordination
• Slurred speech
• Postural hypotension
• Anxiety or panic attacks
• Seizures in patients with existing seizure disorders

Important Precautions

Before dosing on Sativex, inform your doctor if you are taking other medications or herbal supplements. Also, keep the following guidelines in mind:

• Sativex is intended as an oromucosal spray, so it must be absorbed in the lining of the mouth. Spritz it under the tongue or inside the cheek as often as prescribed by your doctor.
• Do not directly spray it into the nose or towards the pharynx. Do not try to inhale the spray.
• Refrain from using it on children under 18 years of age as its safety and efficacy have not been established in adolescents or children.
• Sativex is not recommended for pregnant or nursing women and patients with any of the following health conditions:
  • Ischemic heart disease
  • Arrhythmias
  • Severe hypertension
  • Heart failure
  • Schizophrenia or any other psychotic disorder
• Patients are discouraged from driving vehicles, operating machinery, or engaging in activities requiring unimpaired judgment and motor coordination.

Epidiolex® (Cannabidiol)

Epidiolex is the first FDA-approved cannabis-derived medication in the U.S. It is used to treat severe forms of epilepsy, Lennox-Gastaut syndrome, and Dravet syndrome in patients who are at least two years of age. This medication contains purified cannabidiol (CBD) – the non-psychoactive component of cannabis known for its potent anticonvulsant properties. Hence, patients need not worry about getting high while medicating.

To ensure the safety of the product, GW Research Ltd. studied Epidiolex’s effectiveness using three randomized, double-blind, placebo-controlled clinical trials involving 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. These studies show that Epidiolex can effectively reduce the frequency of seizures. Moreover, it can be used in conjunction with other anticonvulsant medications.

Side Effects

As with other medications, Epidiolex may cause side effects. Be sure to inform your physician if these symptoms are severe or don’t go away:

• Sleepiness
• Diarrhea
• Fatigue
• Insomnia
• Loss of appetite
• Rapid weight loss
• Drooling or excessive saliva
• Problems with walking

Get emergency medical treatment if you experience any of these severe symptoms.

• Rashes
• Hives
• Erythema or redness
• Nausea and vomiting
• Jaundice-like symptoms such as yellow skin or eyes
• Itching
• Unusual darkening of the urine
• Right upper stomach area pain or discomfort
• Fever
• Cough or other signs of infection

Important Precautions

When dosing Epidiolex, follow the following guidelines to ensure safety.

• Inform your doctor if you’re taking other medications or herbal supplements so that he/she could rule out any medication that can trigger adverse drug interaction.
• Epidiolex should be taken twice a day orally, with or without food.
• Take cannabidiol at around the same time(s) every day.
• Do not take more or less than the prescribed dosage.
• Use the oral syringe that came with the medication for measuring the solution for accurate dosing. Do not use a household spoon to measure your dose.
• Do not stop taking Epidiolex without consulting your doctor. Otherwise, you may experience withdrawal symptoms such as new or worsening seizures.

Marinol® and Syndros® (Dronabinol)

Marinol and Syndros are brands of cannabis-based medications containing Dronabinol, a synthetic version of 9-delta-tetrahydrocannabinol (THC). Instead of extracting it from marijuana plants, this substance is synthesized in the laboratory.

Dronabinol (generic name) is used to treat:

• Nausea and vomiting in cancer patients undergoing chemotherapy
• Rapid weight loss due to anorexia nervosa
• Lack of appetite in AIDS patients
• Neuropathic pain associated with multiple sclerosis

Side Effects

Because Dronabinol has the same chemical composition as THC, it also exerts the same effects and adverse reactions. Experiencing any of the following side effects is perfectly normal, albeit a bit uncomfortable:

• Dry mouth and parchedness
• Red eyes
• Drowsiness
• Fatigue
• Headache and lightheadedness
• Dizziness and confusion
• Intense euphoria
• Postural hypotension

When taken in higher doses, the side effects could get more intense. It can cause severe impairments in cognitive and physical functioning, such as follows:

• Memory loss
• Anxiety
• Difficulty concentrating
• Visual and/or auditory hallucinations
• Impairment of motor coordination
• Stomach discomfort

In some cases, the adverse effects could be serious. If you experience any of the following symptoms, call your doctor right away:

• Seizures
• Rapid heartbeat (tachycardia)
• Fainting

Important Precautions

For best results, always stick to your physician’s instructions on when and how often to dose Dronabinol. In general, though, keep the following guidelines in mind:

• Dronabinol comes in either capsule or liquid (solution) form. Both have to be taken orally. It is usually taken 1 to 3 hours before chemotherapy and then every 2 to 4 hours after chemotherapy, for a total of 4 to 6 doses a day.
• The first dose of the solution is usually taken on an empty stomach at least 30 minutes before eating. However, the following doses can be taken with or without food.
• Inform your doctor if you are taking disulfiram, metronidazole, or any other medications, vitamins, and herbal supplements, so that possibilities of drug interaction could be ruled out.
• If you are pregnant or planning to become pregnant, your doctor might opt not to prescribe Dronabinol as it can have adverse effects on your pregnancy.
• Do not breastfeed while you are taking Dronabinol. Wait for nine (9) days before breastfeeding after your last Dronabinol dose.
• Dronabinol may be habit-forming, especially when taken in higher doses over a long period. As such, refrain from dosing more often than prescribed by your doctor.
• Do not stop taking Dronabinol without consulting your doctor. Otherwise, you may experience withdrawal symptoms such as:
  • Irritability
  • Insomnia
  • Fidgeting and restlessness
  • Hot flashes
  • Excessive sweating
  • Runny nose
  • Diarrhea
  • Hiccups
  • Loss of appetite
• If you are about to have surgery, inform the doctor that you are taking Dronabinol.

Cesamet™ (Nabilone)

Cesamet is an FDA-approved synthetic cannabinoid with a chemical structure similar to 9-delta-THC. As a raw material, Nabilone naturally occurs as a polymorphic crystalline powder.

It is used as a treatment for:

• Nausea and vomiting due to chemotherapy in cancer patients who do not respond to conventional antiemetics
• Neuropathic pain in patients with fibromyalgia and multiple sclerosis

Aside from that, it also produces psychoactive effects similar to THC. When taken in the recommended dosage, it alters the patient’s mental state and exerts relaxation, drowsiness, and euphoria. As such, Cesamet should only be used in circumstances that permit close supervision of the patient by a responsible adult.

Side Effects

As with other medications, Cesamet could trigger side effects that could last for 48 to 72 hours after dosing. Such adverse reactions are more common when the drug is taken in higher doses.

• Dry mouth
• Orthostatic hypotension
• Vertigo
• Drowsiness
• Tachycardia or rapid heartbeat
• Euphoria
• Detachment and disorientation
• Depression
• Anxiety, paranoia, or panic attacks
• Impaired memory and cognitive performance
• Decreased ability to control drives and impulses
• Distortions in the perception of time
• Hallucinations or psychosis-like symptoms
• Ataxia or loss of full control of bodily movements

Important Precautions

Cesamet is deemed safe and effective in clinical trials, but to get the best results, keep these points in mind:

• Although synthetically-derived, Cesamet (Nabilone) has the potential to be abused. It could also produce psychological dependence.
• Patients receiving treatment with Cesamet should not drive, operate machinery, or engage in any activity requiring unimpaired cognitive and motor functions.
• Take Nabilone at around the same time every day.
• Do not take Cesamet with alcohol, sedatives, hypnotics, or other psychoactive substances to avoid potentiating effects of Nabilone on the central nervous system.
• Inform your physician if you’re taking other medication, vitamins, psychoactive drugs, or herbal supplements to avoid drug interactions.
• Cesamet should be used with caution in patients with a history of substance abuse since this medication contains a THC-like substance.
• Before dosing on Cesamet, inform your doctor if you are pregnant, lactating, or planning to get pregnant soon.

Dexanabinol (HU-211)

Dexanabinol is a synthetic, terpene-based cannabinoid derivative developed by e-Therapeutics PLC. Unlike most cannabinoid derivatives, though, Dexanabinol does not act as a cannabinoid receptor agonist. Instead, it has NMDA antagonist effects. As such, it does not produce psychotropic effects and is generally well-tolerated in humans. This agent also shows great potential in mitigating various diseases with its neuroprotective, anticonvulsant, anti-inflammatory, and antineoplastic properties.

It protects neuronal cells against the damage of reactive oxygen as well as NMDA and glutamate neurotoxicity. This agent also shows potential in restoring normal apoptotic processes in cancerous cells. This is because it inhibits the activity of nuclear factor kappa B (NF-kB), which plays a key role in the apoptosis and proliferation of cancer cells.

As of December 2004, Denaxabinol completed the Phase III clinical trial involving 846 patients with severe traumatic brain injury. Research findings indicate that the said drug failed to show statistically significant improvement in the late-stage clinical trial. Another Phase I study is underway to test the efficacy of Denaxabinol on the treatment of brain cancer and solid tumors. It is still awaiting results.

HU-331

HU-331 or Cannabidiolquinone (CBDQ) is a quinone anti-carcinogenic drug synthesized from CBD. It shows high efficacy against human cancer cells by inhibiting DNA topoisomerase II (Top2) – an agent that plays a vital role in DNA replication, transcription, and chromosome segregation. When HU-331 inhibits Top2, it induces apoptosis and prevents the replication of cancer cells. And unlike other quinones, it is not cardiotoxic and does not induce the formation of free radicals. It also doesn’t cause damage to DNA.

Although HU-331 has demonstrated efficacy in pre-clinical laboratory studies, it is not approved for use outside laboratory research. However, it is still available for purchase at Cayman Chemical if it is for research.

Call for More Research

More and more researchers are taking an interest in marijuana’s touted medicinal benefits with the gradual yet steadily easing restrictions on cannabis across states. However, with the current number of studies and clinical trials on marijuana’s efficacy and safety in human subjects, it is perhaps too early to say that marijuana’s drug scheduling should be lowered.

DEA and the FDA maintain that researchers must first conduct clinical trials on hundreds to thousands of human subjects to determine the benefits and risks of using the marijuana plant as a medication. Only then can we establish enough scientific data to prove that marijuana’s category should indeed be reduced to Schedule II or lower. For now, let’s take comfort in knowing that cannabis shows immense therapeutic potential and will wait for more large-scale research findings to solidify that claim.