Administration

Administration

The consensus on treatment seems to be the consumption of 50 – 60 grams of oil within 3 months. Initial dose guidelines advise starting with a blob of oil the size of a grain of rice and to build up to a gram a day as soon as possible.

It seems logical to trial different methods of administration and use a combination of them in treatments

Bud Buddies II Cannabis Oil

Sublingual

Sublingual application is simply putting the oil under your tongue, wiki reports “Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster, and it ensures that the substance will risk degradation only by salivary enzymes before entering the bloodstream, whereas orally administered drugs must survive passage through the hostile environment of the gastrointestinal tract, which risks degrading them,……”

Oral

Oral ingestion is very interesting as it creates 11-Hydroxy-THC which is four to five times more psychoactive than Delta 9-THC, putting the oil in capsules aids administration.

Supposotories

People who use cannabis oil suppositories generally report that the uptake is faster and that the effects are stronger and longer lasting

Side Effects

The following is the advice given to people using Sativex® but many of the side-effects will be recognised by people consuming cannabis oil.

4.3 Contraindications

Sativex is contraindicated in patients:

• With hypersensitivity to cannabinoids or to any of the excipients.

• With any known or suspected history or family history of schizophrenia, or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.

• Who are breast feeding (in view of the considerable levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants).

    4.4 Special Warnings And Precautions For Use

Mild or moderate dizziness is commonly reported. This most frequently occurs in the first few weeks of treatment.

Sativex is not recommended for use in children or adolescents below 18 years of age due to lack of safety and efficacy data.

Alterations in pulse rate and blood pressure have been observed following initial dose introduction so caution during initial dose titration is essential. Fainting episodes have been observed with use of Sativex. Use of Sativex is not recommended in patients with serious cardiovascular disease. However, following dosing in healthy volunteers with Sativex up to 18 sprays twice daily, there were no clinically relevant changes in QTc, PR or QRS interval duration, heart rate, or blood pressure.

Until further information is available, caution should be taken when treating patients with a history of epilepsy, or recurrent seizures.

Psychiatric symptoms such as anxiety, illusions, changes in mood, and paranoid ideas have been reported during treatment with Sativex. These are likely to be the result of transient CNS effects and are generally mild to moderate in severity and well tolerated. They can be expected to remit on reduction or interruption of Sativex medication.

Disorientation (or confusion), hallucinations and delusional beliefs or transient psychotic reactions have also been reported and in a few cases a causal association between Sativex administration and suicidal ideation could not be ruled out. In any of these circumstances, Sativex should be stopped immediately and the patient monitored until the symptom has completely resolved.

No specific studies have been carried out in patients with significant hepatic or renal impairment. THC and CBD are metabolised in the liver, and approximately one third of the parent drugs and their metabolites are excreted in the urine (the remainder via the faeces). Several THC metabolites may be psychoactive. Thus, the systemic exposure and the effects of Sativex are dependent on both renal and hepatic function and in patients with significant impaired hepatic or renal function; the effects of Sativex may be exaggerated or prolonged. Frequent clinical evaluation by a clinician is recommended in these patient populations.

Sativex contains approximately 50% v/v of ethanol. Each actuation contains up to 0.04g of ethanol. A small glass of wine (125 mL) of nominal ethanol content 12% v/v would contain approximately 12g ethanol. Most patients respond at doses up to and including 12 sprays a day which would contain less than 0.5 g of ethanol.

There is a risk of an increase in incidence of falls in patients whose spasticity has been reduced and whose muscle strength is insufficient to maintain posture or gait. In addition to an increased risk of falls, the CNS adverse reactions of Sativex could potentially have an impact on various aspects of personal safety, such as with food and hot drink preparation.

Although there is a theoretical risk that there may be an additive effect with muscle-relaxing agents such as baclofen and benzodiazepines, thereby increasing the risk of falls, this has not been seen in clinical trials with Sativex. However, patients should be warned of this possibility.

Although no effect has been seen on fertility, independent research in animals found that cannabinoids affected spermatogenesis. Female patients of child-bearing potential and male patients with a partner of childbearing potential should ensure that reliable contraceptive precautions are maintained for the duration of therapy and for three months after discontinuation of therapy.

Patients who have a history of substance abuse, may be more prone to abuse Sativex as well (see section 5.1).

The abrupt withdrawal of long-term Sativex treatment has not resulted in a consistent pattern or time-profile of withdrawal-type symptoms and the likely consequence will be limited to transient disturbances of sleep, emotion or appetite in some patients. No increase in daily dosage has been observed in long-term use, and patient self-reported levels of ‘intoxication’ are low. For these reasons, dependence on Sativex is unlikely.

Adverse reactions have been reported which could be associated with the route of administration of the medicine. Application site type reactions consisted of mainly mild to moderate stinging at the time of application. Common application site reactions include application site pain, oral pain and discomfort, dysgeusia, mouth ulceration and glossodynia. Two cases of possible leukoplakia were observed but neither was confirmed histologically; a third case was unrelated. In view of this, patients who observe discomfort or ulceration at the site of application of the medicine are advised to vary the site of application within the mouth and should not continue spraying onto sore or inflamed mucous membrane. Regular inspection of the oral mucosa is also advised in long-term administration. If lesions or persistent soreness are observed, medication should be interrupted until complete resolution occurs.

Patients should be advised that if they travel to another country it may not be legal for them to take this medicine into some countries. They should be encouraged to check the legal status before travelling with Sativex.

Pregnancy and lactation: refer to section 4.6.

    4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The two main components of Sativex, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are metabolised by the cytochrome P450 enzyme system.

The inhibitory effects of Sativex on the cytochrome P450 system seen in vitro and in animal models were only seen at exposures significantly higher than the maximum observed in clinical trials.

In an in vitro study with 1:1% (v/v) THC botanical drug substance (BDS) and CBD BDS, no relevant induction of cytochrome P450 enzymes was seen for human CYP1A2, CYP2C9, CYP2C19 and CYP3A4 enzymes in human hepatocytes, at doses of up to 1µM (314 ng/mL).

When Sativex is co-administered with food the mean Cmax and AUC for THC were 1.6- and 2.8-fold higher compared with fasting conditions. Corresponding figures for CBD were 3.3- and 5.1-fold. Concomitant treatment with the CYP3A4 inhibitor ketoconazole produced an increase in Cmax and AUC of THC (1.2- and 1.8-fold, respectively), its primary metabolite (3- and 3.6-fold, respectively) and of CBD (2- and 2-fold, respectively). Therefore, if concomitant drug treatment with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) is started or stopped during treatment with Sativex, a new dose titration may be required.

Following treatment with the CYP3A4 inducer rifampicin reductions in Cmax and AUC of THC (40% and 20% reduction, respectively), its primary metabolite (85% and 87% reduction, respectively) and CBD (50% and 60% reduction, respectively) were observed. Therefore, if concomitant drug treatment with strong enzyme inducers (e.g. rifampicin, carbamazepine, St John’s Wort) is started or stopped during treatment with Sativex, a new dose titration may be required.

Concomitant treatment with the CYP2C19 inhibitor omeprazole resulted in no notable change in any of the pharmacokinetic parameters.

Based on in vitro data an inhibition of p-glycoprotein at the intestinal level by CBD cannot be excluded. Therefore, caution is recommended upon concomitant treatment with digoxin and other drugs being substrates for p-glycoprotein.

Care should be taken with hypnotics, sedatives and drugs with potential sedating effects as there may be an additive effect on sedation and muscle relaxing effects.

Although there has been no greater rate of adverse events in patients already taking anti-spasticity agents with Sativex, care should be taken when co-administering Sativex with such agents since a reduction in muscle tone and power may occur, leading to a greater risk of falls.

Sativex may interact with alcohol, affecting co-ordination, concentration and ability to respond quickly. In general, alcoholic beverages should be avoided whilst using Sativex especially at the beginning of treatment or when changing dose. Patients should be advised that if they do drink alcohol while using Sativex additive CNS effects could increase the risk of falls and other accidents.

    4.6 Pregnancy And Lactation

There is insufficient experience in humans regarding the effects of Sativex on reproduction. Therefore men and women of child bearing potential should take reliable contraceptive precautions for the duration of therapy and for three months after discontinuation of therapy.

Pregnancy

Sativex should not be used during pregnancy unless the potential risks to the fetus and/or embryo are considered to be outweighed by the benefit of treatment.

Lactation

In view of the considerable levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants, Sativex is contraindicated in breast feeding mothers (see section 5.3).

    4.7 Effects On Ability To Drive And Use Machines

Sativex may produce undesirable effects such as dizziness and somnolence which may impair judgement and performance of skilled tasks. Patients should not drive, operate machinery or engage in any hazardous activity if they are experiencing any significant CNS effects such as dizziness or somnolence. Patients should be aware that Sativex has been known to cause a few cases of loss of consciousness.

    4.8 Undesirable Effects

The Sativex clinical program has so far involved over 1500 patients with MS in placebo controlled trials and long-term open label studies in which some patients used up to 48 sprays per day.

The most commonly reported adverse reactions in the first four weeks of exposure were dizziness, which occurs mainly during the initial titration period, and fatigue. These reactions are usually mild to moderate and resolve within a few days even if treatment is continued (see section 4.2). When the recommended dose titration schedule was used, the incidence of dizziness and fatigue in the first four weeks was much reduced.

The frequency of adverse events with a plausible relationship to Sativex, from placebo controlled trials in patients with MS, according to System Organ Classes (SOC) are given below (some of these adverse events may be part of the underlying condition).

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