Sativex: Uses, Dosage & Side Effects

What Is Sativex and What Is It Used For?

Sativex (also known by its international non-proprietary name nabiximols) is a unique pharmaceutical preparation derived from the Cannabis sativa plant. Unlike recreational cannabis products, Sativex is a standardized, quality-controlled medicine containing precisely measured amounts of two key cannabinoids: delta-9-tetrahydrocannabinol (THC) at 27 mg/mL and cannabidiol (CBD) at 25 mg/mL. Each spray delivers 2.7 mg of THC and 2.5 mg of CBD, along with smaller amounts of other naturally occurring cannabinoids, terpenes, and flavonoids from the plant extract.

The primary indication for Sativex is the symptomatic treatment of moderate to severe spasticity in adults with multiple sclerosis. Spasticity is a condition in which muscles become abnormally stiff, tight, or rigid due to disruption of nerve signals in the central nervous system. In MS, the immune system damages the protective myelin sheath surrounding nerve fibers, leading to impaired signaling that can cause increased muscle tone, involuntary muscle contractions, and reduced range of motion. Spasticity affects an estimated 60-80% of people living with MS and can significantly impact mobility, comfort, and quality of life.

Sativex is specifically designed for patients who have already tried other antispasticity medications, such as baclofen, tizanidine, or dantrolene, without achieving satisfactory symptom control. It is prescribed as an add-on therapy, meaning it is used alongside existing treatments rather than as a replacement. The rationale for this positioning reflects the fact that many patients with MS experience refractory spasticity that does not respond adequately to conventional oral antispasticity agents alone.

The 4-Week Trial Period

Treatment with Sativex should only be initiated by a specialist physician experienced in managing MS. Before starting therapy, the specialist will assess the severity of spasticity and review the patient's treatment history to confirm that previous medications have been tried and found insufficient.

Patients then undergo a mandatory 4-week trial period during which the dose is gradually titrated upward and the response is carefully monitored. At the end of this trial, the specialist conducts a formal reassessment. Only patients who demonstrate a clinically meaningful improvement in their spasticity symptoms should continue treatment with Sativex. Evidence from clinical trials suggests that approximately 40-50% of patients are classified as initial responders, and these responders tend to maintain their improvement with continued use.

If no significant benefit is observed after the 4-week trial, Sativex should be discontinued. Continuing treatment in non-responders is unlikely to provide benefit and unnecessarily exposes patients to potential side effects. This responder-enriched approach helps ensure that the medicine is used only in patients most likely to derive meaningful clinical benefit.

What Should You Know Before Taking Sativex?

Before starting treatment with Sativex, it is essential to have a thorough discussion with your prescribing specialist about your complete medical history, current medications, and lifestyle factors. Sativex contains active cannabinoids that interact with the body's endocannabinoid system and can affect multiple organ systems, making it important to identify any conditions or circumstances that could increase the risk of adverse effects.

Contraindications

The contraindication related to psychiatric disorders is particularly important. Cannabinoids can affect the dopaminergic and serotonergic systems in the brain, and there is evidence suggesting that THC exposure may precipitate or exacerbate psychotic episodes in individuals with a predisposition to psychotic illness. Even a family history of schizophrenia or psychosis in a first-degree relative (parent, sibling, or child) is considered a contraindication due to the known genetic component of these disorders.

Warnings and Precautions

Special care and close medical supervision are recommended when using Sativex in the following situations:

• Pregnancy or planning pregnancy: The effects of Sativex on fetal development have not been adequately studied in humans. Animal studies have shown some developmental effects at high doses, so Sativex should only be used during pregnancy if the potential benefit clearly outweighs the risk
• Patients under 18 years: Safety and efficacy have not been established in children and adolescents
• Epilepsy or seizure disorders: Cannabinoids may lower the seizure threshold in some individuals, although CBD itself has anticonvulsant properties
• Moderate to severe kidney disease: Limited data are available on the use of Sativex in patients with significant renal impairment
• Moderate to severe liver disease: THC and CBD are extensively metabolized by the liver, and impaired hepatic function may lead to increased drug exposure and enhanced effects
• Serious cardiovascular disease: Patients with angina, history of myocardial infarction, poorly controlled hypertension, or cardiac rhythm disturbances require careful monitoring because cannabinoids can affect heart rate and blood pressure
• Elderly patients: Older adults may be more susceptible to the central nervous system effects of Sativex, including dizziness and sedation, which can increase fall risk. Particular caution is advised for those with difficulties performing daily activities
• History of substance abuse: Although the abuse potential of Sativex is considered low compared to recreational cannabis due to its controlled delivery and CBD content, patients with a history of drug or substance misuse should be closely monitored

Pregnancy and Breastfeeding

Do not use Sativex during pregnancy unless your doctor has specifically recommended it. The active cannabinoids in Sativex can cross the placental barrier, and their effects on fetal development are not fully understood. Animal reproductive studies have produced some findings of concern at high doses, though their relevance to human pregnancy at therapeutic doses remains uncertain.

Sativex is strictly contraindicated during breastfeeding. THC and CBD are lipophilic compounds that are known to accumulate in breast milk, where they could be ingested by the nursing infant. The potential effects of cannabinoid exposure on infant brain development are a significant concern, and therefore breastfeeding must be avoided entirely during treatment.

Driving and Operating Machinery

You must not drive a vehicle or operate tools or machinery when you first start treatment with Sativex, until a stable daily dose has been established and you know how the medication affects you. Sativex can cause drowsiness, dizziness, and impaired judgment, which may reduce your ability to perform tasks requiring alertness. Isolated cases of brief loss of consciousness have also been reported.

Even after you have adjusted to Sativex and your dosage is stable, you should not drive or use machinery if Sativex causes effects such as drowsiness or dizziness that could impair your ability to perform such activities safely. Be aware that driving while using Sativex may be subject to specific legal regulations in certain countries, and the presence of THC in blood or urine may affect roadside drug testing results.

Traveling Internationally

Before traveling abroad with Sativex, verify that it is legal to carry this medication in all countries you will pass through, including transit countries. Sativex is classified as a controlled substance, and its legal status varies considerably between jurisdictions. Some countries have strict anti-cannabis laws that do not differentiate between prescribed pharmaceutical cannabis products and recreational cannabis. Carrying a letter from your prescribing physician, along with a copy of your prescription, is recommended but may not provide legal protection in all jurisdictions.

Alcohol and Propylene Glycol Content

Sativex contains up to 40 mg of ethanol (alcohol) per spray dose. At the maximum recommended dose of 12 sprays per day, this amounts to approximately 480 mg of ethanol, equivalent to about 10 mL of beer or 5 mL of wine. While this is a small amount that typically does not produce noticeable effects on its own, patients should be aware that consumption of alcoholic beverages while using Sativex may enhance the effects of both substances, including impaired balance, coordination, and reaction time, increasing the risk of falls and accidents. Alcohol should generally be avoided during treatment, especially during the initial titration period.

Each spray also contains 52 mg of propylene glycol, which may cause mild irritation of the oral mucosa in some individuals.

How Does Sativex Interact with Other Drugs?

THC and CBD, the active cannabinoids in Sativex, are metabolized by several cytochrome P450 enzymes in the liver, including CYP2C9, CYP3A4, and CYP2C19. They can also inhibit or induce certain CYP enzymes, potentially altering the blood levels and effects of co-administered medications. It is essential to inform your doctor and pharmacist about all medications you are taking, including over-the-counter drugs and herbal supplements, before starting Sativex.

If you see different doctors or are admitted to hospital, always inform the medical team that you are taking Sativex, as this information is critical for safe prescribing decisions.

Major Interactions

Minor Interactions

What Is the Correct Dosage of Sativex?

The optimal dose of Sativex varies from person to person. The goal of the titration process is to find the number of sprays per day that provides the best relief of spasticity symptoms while minimizing side effects. Always use Sativex exactly as your specialist has prescribed. If you are unsure about any aspect of your dosing, consult your doctor or pharmacist.

Sativex should only be used inside the mouth, either sprayed on the inside of the cheek or under the tongue. You may take it with or without food, but be aware that food can affect how much of the medication is absorbed. For consistency, try to always take Sativex in the same way relative to meals.

Titration Schedule for Adults

How to Use the Spray

When opening a new bottle, remove it from the refrigerator and write the opening date on the label. The bottle should be used within 6 weeks (42 days) of opening. Shake the bottle gently before use, remove the protective cap, and perform 2-3 test sprays into a tissue when using a new bottle. Point the spray nozzle under your tongue or toward the inside of your cheek, and press firmly once. Replace the cap after each use.

If you accidentally spray into your eyes, rinse immediately with water. Do not inhale the spray. Keep the spray away from children, pets, open flames, and heat sources. Each bottle contains up to 90 metered sprays after the initial priming sprays. When the bottle starts to run low, the sound and feel of the spray may change, indicating it is time to open a new bottle.

Children and Adolescents

Sativex is not approved for use in patients under 18 years of age. The safety and efficacy of Sativex in children and adolescents have not been established in clinical trials, and its effects on the developing brain and endocannabinoid system are not fully understood.

Elderly Patients

No specific dose adjustment is recommended for elderly patients. However, older adults may be more sensitive to the effects of Sativex, particularly dizziness, sedation, and impaired balance. The dose titration should be carried out with extra caution in this population, and patients should be carefully monitored for falls and other adverse events. Elderly patients with difficulty performing daily activities such as preparing hot food and drinks should exercise particular care.

Missed Dose

If you forget a spray, take it when you remember or when you next need it. Do not take a double dose to compensate for a missed one. The effects of Sativex build up over time, so an occasional missed spray is unlikely to cause significant fluctuations in symptom control.

Overdose

Stopping Treatment

If you decide to stop using Sativex for any reason, inform your doctor. Although Sativex does not typically cause physical dependence comparable to some other controlled substances, abruptly stopping the medication may temporarily affect sleep, appetite, or mood. These withdrawal-like effects are generally mild and short-lived. Spasticity symptoms usually return gradually after discontinuation.

What Are the Side Effects of Sativex?

Like all medicines, Sativex can cause side effects, although not everyone experiences them. Most side effects occur during the initial titration phase when the body is adjusting to the medication, and they typically diminish as treatment continues. If you experience troublesome side effects, reducing the number of daily sprays or temporarily stopping treatment usually resolves the problem.

Side effects are most likely to occur during the initial dose titration period. If you experience any of the common side effects, reduce the number of sprays per day until you find the dose that provides the best symptom relief with the fewest side effects. If you develop redness, swelling, or peeling skin at a spray site in your mouth, avoid spraying on that area until it has healed.

It is important to report any suspected side effects to your healthcare provider. Post-marketing surveillance of side effects helps regulatory authorities continuously monitor the benefit-risk profile of the medication and may lead to important safety updates.

How Should You Store Sativex?

Proper storage of Sativex is essential to maintain the stability and potency of the active cannabinoids. Unopened spray bottles must be stored upright in their original outer packaging inside a refrigerator at 2-8°C (36-46°F). If Sativex is not stored in the refrigerator prior to opening, the medication may lose its effectiveness, potentially reducing the therapeutic benefit.

Once opened, the spray bottle should be stored upright at room temperature, not exceeding 25°C (77°F). An opened bottle must be used within 42 days (6 weeks). Write the date of opening on the label provided so you can track when the bottle expires. Do not use the spray after this period has elapsed.

Always check the expiration date printed on the label (marked "EXP") before using Sativex. The expiration date refers to the last day of the indicated month. Keep this medication out of the sight and reach of children. Dispose of unused or expired medication according to your local pharmacy's guidance rather than throwing it in household waste or flushing it down the drain, as this helps protect the environment.

What Does Sativex Contain?

Sativex is a standardized pharmaceutical preparation derived from the leaves and flowers of the Cannabis sativa L. plant. The active substances are two cannabis extracts: one rich in THC and one rich in CBD. Each milliliter of solution contains 38-44 mg and 35-42 mg of these two extracts respectively, corresponding to 27 mg/mL of delta-9-tetrahydrocannabinol (THC) and 25 mg/mL of cannabidiol (CBD). Each 100-microliter metered spray delivers approximately 2.7 mg of THC and 2.5 mg of CBD.

In addition to THC and CBD, the cannabis extract contains smaller quantities of other naturally occurring cannabinoids, terpenes, and flavonoids from the plant material. The excipients (inactive ingredients) are ethanol (alcohol), propylene glycol, and peppermint oil, which is added for flavoring and to help mask the taste of the cannabis extract.

Packaging and Appearance

Sativex is a golden-brown solution supplied in 10 mL amber glass spray bottles fitted with a metering pump mechanism. The pump is protected by a plastic cap. Each bottle provides up to 90 metered sprays after the initial 3 priming sprays. Sativex is available in packs of 3 spray bottles. The marketing authorization holder is Jazz Pharmaceuticals Ireland Ltd, Dublin, Ireland.