Pure and Organic CBD & and Hemp Products

Effective medicine provided by mother nature

  • Powerful relaxant

  • Strong painkiller

  • Stress reduction
  • Energy booster

Why CBD?

More and more renowned scientists worldwide publish their researches on the favorable impact of CBD on the human body. Not only does this natural compound deal with physical symptoms, but also it helps with emotional disorders. Distinctly positive results with no side effects make CBD products nothing but a phenomenal success.

This organic product helps cope with:

  • Tight muscles
  • Joint pain
  • Stress and anxiety
  • Depression
  • Sleep disorder

Range of Products

We have created a range of products so you can pick the most convenient ones depending on your needs and likes.

CBD Capsules Morning/Day/Night:

CBD Capsules

These capsules increase the energy level as you fight stress and sleep disorder. Only 1-2 capsules every day with your supplements will help you address fatigue and anxiety and improve your overall state of health.

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CBD Tincture

CBD Tincture

No more muscle tension, joints inflammation and backache with this easy-to-use dropper. Combined with coconut oil, CBD Tincture purifies the body and relieves pain. And the bottle is of such a convenient size that you can always take it with you.

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Pure CBD Freeze

Pure CBD Freeze

Even the most excruciating pain can be dealt with the help of this effective natural CBD-freeze. Once applied on the skin, this product will localize the pain without ever getting into the bloodstream.

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Pure CBD Lotion

Pure CBD Lotion

This lotion offers you multiple advantages. First, it moisturizes the skin to make elastic. And second, it takes care of the inflammation and pain. Coconut oil and Shia butter is extremely beneficial for the health and beauty of your skin.

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WHY SHOULD I VAPE CBD OIL?

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14.03.2019

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  • had r/cannabis with high strains - anyone extracts, (cannabidiol) Has with experiences CBD CB any or
  • There was a problem providing the content you requested
  • Why Does THC Get You High But Not CBD?
  • In just a few years, cannabidiol (CBD) has become immensely popular around the world. First of all, concentrated extracts allow the consumption of a large dose of . hemp is allowed only with the intent to produce fibers or seeds. . Additionally, as many as 26/46 samples (57%) had a THC content > 1%. In , the first cannabinoid receptor was identified (CB1) (Howlett et al ) and . Cannabidiol, a non-euphoriant phytocannabinoid common in certain strains, shares While THC has no activity at vanilloid receptors, CBD, like AEA, is a TRPV1 Initial experiences with medicinal extracts of cannabis for chronic pain. In a clinical trial THC did not have any significant effect on ongoing and . A mixture of mg THC and mg cannabidiol (CBD) lowered spasm .. Cohen C., Perrault G., Voltz C., Steinberg R., Soubrie P. SR, a central cannabinoid (CB(1)) .. Initial experiences with medicinal extracts of cannabis for chronic pain.

    had r/cannabis with high strains - anyone extracts, (cannabidiol) Has with experiences CBD CB any or

    Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease, epilepsy Parkinson's disease PD is a chronic, progressive neurodegenerative disorder. Bipolar disorder, schizophrenia, post-traumatic stress disorder PTSD , depression, anxiety, insomnia Cannabis use is common in patients with bipolar disorder, and anecdotal reports suggest that some patients use marijuana to alleviate symptoms of both mania and depression.

    Asthma, cardiovascular disorders, glaucoma Asthma is a chronic disease of the respiratory system in which the airway occasionally constricts, becomes inflamed, and is lined with excessive amounts of mucus. Cancer The antiproliferative action of cannabinoids on cancer cells was first noticed in the s.

    Conclusion Many drugs used today can cause addiction and are misused and abused, for example opiates, cocaine, benzodiazepines, barbiturates, cholinergic agonists, ketamine, , dopaminergic agonists, amphetamines, and others. Early medical use of cannabis. Untersuchung der Cannabis sativa. Repertorium fur die Pharmacie. Note sur le haschisch. A historical overview of chemical research on cannabinoids. Isolation, structure and partial synthesis of the active constituent of hashish.

    J Am Chem Soc. Marihuana, an annotated bibliography. Withdrawal symptoms in cannabis indica addicts. The addictive potential of cannabis.

    Clinical studies of cannabis tolerance and dependence. Ann N Y Acad Sci. Treatment of cannabis use disorders: Cannabis addiction and Telic Dominance Scale.

    Clinical trial of abstinencebased vouchers and cognitive-behavioral therapy for cannabis dependence. J Consult Clin Psychol. Addictive potential of cannabinoids: Failure of Delta 9 -tetrahydrocannabinol and CP 55, to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys.

    Endocannabinoid system and alcohol addiction: Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice. SR, a central cannabinoid CB 1 receptor antagonist, blocks the motivational and dopaminereleasing effects of nicotine in rats. The diagnosis of alcohol and cannabis dependence addiction in cocaine dependence addiction.

    Behavioral effects of cocaine alone and in combination with ethanol or marijuana in humans. Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers. Involvement of cannabinoid CB1 receptors in drug addiction: Rimonabant, a CB1 antagonist, blocks nicotineconditioned place preferences. Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: The role of the cannabinoid system in nicotine addiction.

    Successful control of lipids, kilos and cigarettes]. Advances in pharmacotherapy for tobacco dependence. Expert Opin Emerg Drugs. Expert Opin Investig Drugs. Adenosine A2a blockade prevents synergy between mu-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.

    The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: Cell Mol Life Sci. Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther. Cognitive functioning of longterm heavy cannabis users seeking treatment. Chronic cognitive impairment in users of 'ecstasy' and cannabis.

    Cannabis use, cognitive performance and mood in a sample of workers. Long-term effects of frequent cannabis use on working memory and attention: Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. A literature review of the consequences of prenatal marihuana exposure.

    An emerging theme of a deficiency in aspects of executive function. Cannabis, the mind and society: Cannabis and cognitive dysfunction: The psychotomimetic effects of intravenous deItatetrahydrocannabinol in healthy individuals: Amotivational syndrome in organic solvent abusers.

    Characteristics of abnormal behavior induced by delta 9-tetrahydrocannabinol in rats. Psychiatric aspects of cannabis use in adolescents and young adults. Related, induced and associated psychiatric disorders to cannabis. Operant acquisition of marihuana in man. Cannabis, motivation, and life satisfaction in an internet sample. Subst Abuse Treat Prev Policy. Endocannabinoids in the regulation of appetite and body weight.

    Endocannabinoids in appetite control and the treatment of obesity. Genetic variations at the endocannabinoid type 1 receptor gene CNR1 are associated with obesity phenotypes in men. J Clin Endocrinol Metab. Lack of tolerance to the suppressing effect of rimonabant on chocolate intake in rats. The role of CB1 receptors in sweet versus fat reinforcement: SR , a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Efficacy of rimonabant and other cannabinoid CB1 receptor antagonists in reducing food intake and body weight: Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors.

    Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: Clinical trials update and cumulative meta-analyses from the American College of Cardiology: Eur J Heart Fail.

    Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: Rimonabant in obese patients with type 2 diabetes. Am J Health Syst Pharm. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J Pain Symptom Manage. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Dronabinol effects on weight in patients with HIV infection.

    The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. Cannabinoids in the treatment of the cachexiaanorexia syndrome in palliative care patients.

    A phase II study of deltatetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. Mechanism of action of cannabinoids: An efficient new cannabinoid antiemetic in pediatric oncology. Cannabinoids for control of chemotherapy induced nausea and vomiting: Therapeutic potential of cannabinoids in trigeminal neuralgia.

    Cannabinoids block release of serotonin from platelets induced by plasma from migraine patients. Int J Clin Pharmacol Res. Are oral cannabinoids safe and effective in refractory neuropathic pain? Lack of analgesic efficacy of oral deItatetrahydrocannabinol in postoperative pain. Pain relief with oral cannabinoids in familial Mediterranean fever. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: Does the cannabinoid dronabinol reduce central pain in multiple sclerosis?

    Randomised double blind placebo controlled crossover trial. Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis - secondary publication.

    The analgesic properties of deItatetrahydrocannabinol and codeine. Analgesic effect of deItatetrahydrocannabinol. Cannabis use for chronic non-cancer pain: Cannabis use in HIV for pain and other medical symptoms. Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: Cannabimimetic properties of ajulemic acid.

    A tale of two cannabinoids: Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. Initial experiences with medicinal extracts of cannabis for chronic pain: Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Combined cannabinoid therapy via an oromucosal spray. Cannabinoids for the treatment of pain: An update on recent clinical trials.

    Dexanabinol HU effect on experimental autoimmune encephalomyelitis: Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation.

    Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. Changes in CB1 receptors in motor-related brain structures of chronic relapsing experimental allergic encephalomyelitis mice. Marihuana as a therapeutic agent for muscle spasm or spasticity. Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors.

    DeltaTHC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse. Nabilone in the treatment of multiple sclerosis. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis. Treatment of human spasticity with deltatetrahydrocannabinol. The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: Int J Clin Pharmacol Ther.

    Tremor in multiple sclerosis. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Tetrahydrocannabinol for tremor in multiple sclerosis. The effect of cannabis on tremor in patients with multiple sclerosis. Suppression of pendular nystagmus by smoking cannabis in a patient with multiple sclerosis. The effect of cannabis on urge incontinence in patients with multiple sclerosis: Curr Opin Investig Drugs.

    Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on patients.

    Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis CAMS study: Cannabinoids in multiple sclerosis CAMS study: J Neurol Neurosurg Psychiatry. From anecdotal evidence of cannabinoids in multiple sclerosis to emerging new therapeutical approaches.

    Cannabinoids in MS - are we any closer to knowing how best to use them? The endocannabinoid pathway in Huntington's disease: Cannabinoid system and neuroinflammation: Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: Neuroprotective cannabinoid receptor antagonist SRA prevents downregulation of excitotoxic NMDA receptors in the ischemic penumbra.

    Dexanabinol HU in the treatment of severe closed head injury: Efficacy and safety of dexanabinol in severe traumatic brain injury: Cannabinoid-based drugs as anti-inflammatory therapeutics. Anti-inflammatory property of the cannabinoid agonist WIN in a rodent model of chronic brain inflammation. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Involvement of the cannabimimetic compound, N-palmitoyl-ethanoIamine, in inflammatory and neuropathic conditions: Review of the available pre-clinical data, and first human studies.

    Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Effect of the cannabinoid CB1 receptor antagonist rimonabant on nociceptive responses and adjuvant-induced arthritis in obese and lean rats.

    CB1 cannabinoid receptor signalling in Parkinson's disease. The cannabinoid receptor agonist WIN 55, reduces D2, but not D1, dopamine receptor-mediated alleviation of akinesia in the reserpine-treated rat model of Parkinson's disease. Effects of levodopa on endocannabinoid levels in rat basal ganglia: Effects of rimonabant, a selective cannabinoid CB1 receptor antagonist, in a rat model of Parkinson's disease. High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson's disease patients.

    Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson's disease: DeIta9-tetrahydrocannabinol improves motor control in a patient with musician's dystonia. Cannabis for dyskinesia in Parkinson disease: Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease.

    Survey on cannabis use in Parkinson's disease: AIsasua del Valle A. Implication of cannabinoids in neurological diseases. An overview of Parkinson's disease and the cannabinoid system and possible benefits of cannabinoid-based treatments.

    Potential role of cannabinoids in Parkinson's disease. The pattern of neurodegeneration in Huntington's disease: Selective vulnerability in Huntington's disease: Loss of cannabinoid receptors in the substantia nigra in Huntington's disease. Arvanil, a hybrid endocannabinoid and vanilloid compound, behaves as an antihyperkinetic agent in a rat model of Huntington's disease.

    The cannabinoid receptor agonist WIN 55, attenuates the effects induced by quinolinic acid in the rat striatum. Controlled clinical trial of cannabidiol in Huntington's disease. Cannabinoids reduce symptoms of Tourette's syndrome.

    Delta 9-tetrahydrocannabinol THC is effective in the treatment of tics in Tourette syndrome: Tourette syndrome is not caused by mutations in the central cannabinoid receptor CNR1 gene. Marijuana in the management of amyotrophic lateral sclerosis. Am J Hosp Palliat Care. Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice. AM , a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis.

    The CB2 cannabinoid agonist AM prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. Survey of cannabis use in patients with amyotrophic lateral sclerosis.

    A molecular link between the active component of marijuana and Alzheimer's disease pathology. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Int J Geriatr Psychiatry.

    DeItatetrahydrocannabinol for nighttime agitation in severe dementia. Anticonvulsant activity of four oxygenated cannabidiol derivatives. Res Commun Chem Pathol Pharmacol. Antiepileptic potential of cannabidiol analogs. Structure-anticonvulsant activity relationships of cannabidiol analogs. Anticonvulsant effect of cannabidiol. S Afr Med J.

    Cannabidiol-antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. Anticonvulsant interaction of cannabidiol and ethosuximide in rats.

    Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy. Cannabinoid CB1 receptor antagonists cause status epilepticus-Iike activity in the hippocampal neuronal culture model of acquired epilepsy. Arachidonyl-2'-chIoroethyIamide, a highly selective cannabinoid CB1 receptor agonist, enhances the anticonvulsant action of valproate in the mouse maximal electroshock-induced seizure model.

    Grand mal convulsions subsequent to marijuana use. Chronic administration of cannabidiol to healthy volunteers and epileptic patients.

    Cannabinoids in bipolar affective disorder: The use of cannabis as a mood stabilizer in bipolar disorder: Towards a cannabinoid hypothesis of schizophrenia: Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: Impact of cannabis use.

    Clinical features of cannabis psychosis in schizophrenia patients. Cannabis and acute psychosis. Schizophrenia and cannabis consumption: A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: Implications for the concept of cannabis psychosis.

    Lifetime positive symptoms in patients with schizophrenia and cannabis abuse are partially explained by co-morbid addiction. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder.

    Antipsychotic effect of cannabidiol. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. Cannabidiol monotherapy for treatment-resistant schizophrenia. Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Inhibition of fatty-acid amide hydrolase accelerates acquisition and extinction rates in a spatial memory task.

    Differential response to acute and repeated stress in cannabinoid CB1 receptor knockout newborn and adult mice. Drug use and validity of substance use self-reports in veterans seeking help for posttraumatic stress disorder.

    Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene CNR1. Antianxiety effect of cannabidiol in the elevated plus-maze. Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze. In addition, THC C max values were significantly greater among frequent smokers compared to occasional smokers after smoking and vapourization only, and hydroxy-THC C max values were significantly greater among frequent smokers regardless of route of administration.

    Oro-mucosal administration of nabiximols is also amenable to self-titration Reference Reference Reference Reference In humans, rectal doses of 2. Cannabinoids are highly hydrophobic, making transport across the aqueous layer of the skin the rate-limiting step in the diffusion process Reference No clinical studies have been published regarding the percutaneous absorption of cannabis-containing ointments, creams, or lotions.

    However, some pre-clinical research has been carried out on transdermal delivery of synthetic and natural cannabinoids using a dermal patch Reference Reference Due to its lipophilicity, it is taken up primarily by fatty tissues and highly perfused organs such as the brain, heart, lung, and liver Reference The apparent average volume of distribution of CBD is Pre-clinical studies in mice suggest a more rapid penetration of hydroxy-THC into the brain compared to the parent compound, on the order of 6: This finding lends further support to the evidence on the distribution, accumulation, and storage of THC and metabolites in the adipose tissue and the slow release of THC and metabolites from adipose tissue stores back into the bloodstream Reference Residual THC in plasma likely coming from bodily adipose stores detected weeks after last smoking episode may be associated with persisting psychomotor impairment in frequent chronic cannabis smokers according to the study authors Reference Most cannabinoid metabolism occurs in the liver, and different metabolites predominate depending on the route of administration Reference 78 Reference CBD undergoes extensive Phase I metabolism, with a reported 30 different metabolites in the urine, and the most abundant metabolites are hydroxylated 7 or 11 -carboxy derivatives of CBD, with 7 or 11 -hydroxy CBD as a minor metabolite Reference 78 Reference Reference Xenobiotics are not only metabolized by CYPs but they also modulate the expression level and activity of these enzymes; CYPs are therefore a focal point in drug-drug interactions and adverse drug reactions Reference Please see Section 6.

    While few clinical studies have specifically sought to evaluate cannabis-drug interactions per se, many, if not most, studies investigating the therapeutic effects of cannabis e. Cannabis smoking, as well as orally administered dronabinol may also affect the pharmacokinetics of anti-retroviral medications, although no clinically significant short-term impacts on anti-retroviral effects were noted Reference In addition, and as seen with tobacco smoke, cannabis smoke has the potential to induce CYP1A2 thereby increasing the metabolism of xenobiotics biotransformed by this isozyme such as theophylline Reference or the anti-psychotic medications clozapine or olanzapine Reference Further detailed information on drug-drug interactions can be found in Section 6.

    Similar results were obtained with intravenous THC administration Reference Following oxidation, the phase II metabolites of the free drug or hydroxylated-THC appear to be glucuronide conjugates Reference Peak plasma values of the psycho-inactive metabolite, norcarboxy THC, occur 1.

    The plasma levels of active hydroxy metabolite, achieved through oral administration, are about three times higher than those seen with smoking Reference Concentrations of both parent drug and metabolite peak between approximately 2 to 4 h after oral dosing, and decline over several days Reference A study that characterized cannabinoid elimination in blood from 30 male daily cannabis smokers during monitored sustained abstinence for up to 33 days on a closed residential unit found that low levels approx.

    Following oral administration, THC and its metabolites are also excreted in both the feces and the urine Reference 78 Reference A large portion of administered CBD is excreted intact or as its glucuronide Reference Reference Reference The variability in terminal half-life measurements are related to the dependence of this measure on assay sensitivity, as well as on the duration and timing of blood measurements Reference Low levels of THC metabolites have been detected for more than five weeks in the urine and feces of cannabis users Reference Like THC, the decline of CBD levels is also multi-phasic, and the half-life of CBD in humans after smoking has been estimated at 27 - 35 h, and 2 - 5 days after oral administration Reference Reference Reference More limited information is available for inhaled cannabis Reference 58 Reference A dosing interval of 1 h with this dose would give a "continuous high", and the recovery time after the last dose would be min i.

    One clinical study reported a peak increase in heart rate and perceived "good drug effect" within 7 min after test subjects smoked a 1 g cannabis cigarette containing either 1. Compared to the placebo, both doses yielded statistically significant differences in subjective and physiological measures; the higher dose was also significantly different from the lower dose for subjective effects, but not physiological effects such as an effect on heart rate.

    The equilibration half-life estimate for heart rate was approximately 7 min, but varied between 39 and 85 min for various CNS parameters Reference According to this model, the effects on the CNS developed more slowly and lasted longer than the effect on heart rate.

    Subjects reported smoking a mean of one joint per day in the previous 14 days prior to the initiation of the study range: During the study, subjects smoked one cannabis cigarette mean weight 0. According to the authors of the study, the pharmacodynamic-pharmacokinetic relationship displayed a counter-clockwise hysteresis i. THC , the pharmacological effect is greater at a later time point than at an earlier one for all measured subjective effects e. This particular kind of relationship demonstrates a lack of correlation between blood concentrations of THC and observed effects, beginning immediately after the end of smoking and continuing during the initial distribution and elimination phases.

    Following the start of cannabis smoking, heart rate increased significantly at the 30 min time point, diastolic blood pressure decreased significantly only from the 30 min to 1 h time point, and systolic blood pressure and respiratory rate were unaffected at any time. A study that examined the acute subjective effects associated with smoked cannabis at three different doses i.

    In addition, the study also showed that higher doses of THC were associated with longer duration of subjective effects. Findings from the study showed that the time required to reach a maximal "high" rating was slightly delayed 11 - 16 min compared to the time required to reach the peak THC serum concentration.

    The "high" rating declined after reaching the peak within the first 3. Scores on the VAS for "dizziness", "dry mouth", "palpitations", "impaired memory and concentration", "down", "sedated", and "anxious feelings" reached a maximum within the first 2 h post-dose and these effects were dose-dependent. With a dose of A dose of Finally, a THC dose of The THC-induced decrease in stimulation i. In fact, sedation was increased by almost six-fold compared to placebo.

    The low THC dose was associated with the highest ratings of "like the effects of the drug" and "want more of this drug". Maximal subjective "high" ratings occurred at 60 min following beginning of inhalation. One clinical study reported that ad libitum vapourization of mg cannabis containing a low-dose 2. Subjective effects were then measured at several time points and effects were correlated with concentrations of cannabinoids in oral fluid and blood.

    There were no significant differences between the effects seen with the low 2. Vapourized cannabis significantly increased measures of "stoned" and "sedated" immediately post-dose and lasted 3. Feelings of "anxious" showed significant cannabis-dose effects through 1.

    Effects and time course of effects were similar between vapourized and smoked cannabis. Another study measured 17 different psychoactive effects as a function of THC dose and time in vapourized cannabis Reference Plasma hydroxy-THC C max for the 2. The lower dose produced effects lower than that for the high dose and placebo effects were lower than both active doses for "any drug effect", "good drug effect", "high", "impaired", "stoned", "sedated" and "changes perceiving space".

    For "bad drug effect", "like the drug", "nauseous", "changes perceiving time", ratings with placebo were significantly lower than both active doses. The higher dose 6. There was a clear dose-response effect for the majority of psychoactive effects.

    Increases in systolic blood pressure occurred with low 5 mg and high 15 mg oral doses of THC, as well as low 5. In contrast, diastolic blood pressure decreased between 4 and 8 h after dosing. Heart rate increased after all active treatments. A subjective feeling of a "high" was reported to be significantly greater after 15 mg oral THC compared to placebo and to 5 mg oral THC. In contrast, neither the high nor the low doses of oro-mucosal nabiximols were reported to produce a statistically significant subjective "high" feeling.

    Study subjects reported being most "anxious" approximately 4 h after administration of 5 mg oral THC, 3 h after 15 mg oral THC, 5. All active drug treatments induced significantly more anxiety compared to placebo. After 15 mg oral THC, the concentration of THC in plasma was observed to have a weak, but statistically significant, positive correlation with systolic and diastolic blood pressure, "good drug effect", and "high".

    After high-dose oro-mucosal nabiximols, positive correlations were also observed between plasma THC concentrations and "anxious", "good drug effect", "high", "stimulated", and M-scale marijuana-scale scores. Consistent with other studies, the authors of this study reported that linear correlations between plasma THC concentrations and physiological or subjective effects were weak.

    Lastly, although CBD did not appear to significantly modulate the effects of THC, the authors suggested it might have attenuated the degree of the subjective "high". A dose run-up clinical study looking at the pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of THC i.

    There was also substantial variability for T max both within and between subjects with an overall median of 3. THC dose-dependently elevated heart rate, and systolic blood pressure dropped at the lower dose i.

    No changes were noted for diastolic blood pressure. Tolerance, as defined by the Liaison Committee on Pain and Addiction a joint committee with representatives from the American Pain Society, the American Academy of Pain Medicine, and the American Society of Addiction Medicine is a state of adaptation in which exposure to the drug causes changes that result in a diminution of one or more of the drug's effects over time Reference Tolerance to the effects of cannabis or cannabinoids appears to result mostly from pharmacodynamic rather than pharmacokinetic mechanisms Reference Pre-clinical studies indicate that pharmacodynamic tolerance is mainly linked to changes in the availability of the cannabinoid receptors, principally the CB 1 receptor, to signal.

    There are two independent but interrelated molecular mechanisms producing these changes: Studies have reported that CB 1 receptors in the caudate-putamen and its projection areas e.

    CB 1 receptors located in the striatum are also less susceptible to desensitization and downregulation relative to the hippocampus Reference One clinical study showed that chronic cannabis use was associated with a global decrease in CB 1 receptor availability in the brain with significant decreases in CB 1 receptor availability in the temporal lobe, anterior and posterior cingulate cortices, and the nucleus accumbens Reference Furthermore, a couple of clinical studies have examined the time course of changes in the availability of CB 1 receptors following chronic THC administration and abstinence Reference Reference In the second study, cannabis dependence with chronic, moderate daily cannabis smoking was associated with CB 1 receptor downregulation i.

    CB 1 receptor downregulation began to reverse rapidly upon termination of cannabis use within two days , and after 28 days of continuous monitored abstinence CB 1 receptor availability was not statistically significantly different from that of healthy controls although CB 1 receptor availability never reached the levels seen with healthy controls.

    CB 1 receptor availability was also negatively correlated with cannabis dependence and withdrawal symptoms. The observed regional variations in cellular adaptations to THC in the brain may also generalize to other tissues or organs, explaining why tolerance develops to some of the effects of cannabis and cannabinoids but not to other effects. In animal models, the magnitude and time-course of tolerance appear to depend on the species, the cannabinoid ligand, the dose and duration of the treatment, and the measures employed to determine tolerance to cannabinoid treatment Reference Tolerance to most of the effects of cannabis and cannabinoids can develop after a few doses, and it also disappears rapidly following cessation of administration Reference Tolerance has been reported to develop to the effects of cannabis on perception, psychoactivity, euphoria, cognitive impairment, anxiety, cortisol increase, mood, intraocular pressure IOP , electroencephalogram EEG , psychomotor performance, and nausea; some have shown tolerance to cardiovascular effects while others have not Reference Reference Reference There is also some evidence to suggest that tolerance can develop to the effects of cannabis on sleep reviewed in Reference As mentioned above, the dynamics of tolerance vary with respect to the effect studied; tolerance to some effects develops more readily and rapidly than to others Reference Reference However, tolerance to some cannabinoid-mediated therapeutic effects i.

    According to one paper, in the clinical setting, tolerance to the effects of cannabis or cannabinoids can potentially be minimized by combining lower doses of cannabis or cannabinoids along with one or more additional therapeutic drugs Reference One study reported that tolerance to some of the effects of cannabis, including tolerance to the "high", developed both when THC was administered orally 30 mg; q.

    There was no diminution of the appetite-stimulating effect from either route of administration. A clinical study that evaluated the effects of smoked cannabis on psychomotor function, working memory, risk-taking, subjective and physiological effects in occasional and frequent cannabis smokers following a controlled smoking regimen reported that when compared to frequent smokers, occasional smokers showed significantly more psychomotor impairment, more significant impairment of spatial working memory, significantly increased risk-taking and impulsivity, significantly higher scores for "high" ratings, for "stimulated" ratings, and more anxiety Reference Compared with frequent smokers, occasional smokers had significantly increased heart rates relative to baseline and higher systolic and diastolic blood pressure just after dosing.

    These findings suggest that frequent cannabis users can develop some tolerance to some psychomotor impairments despite higher blood concentrations of THC.

    Occasional smokers also reported significantly longer and more intense subjective effects compared with frequent smokers who had higher THC concentrations suggesting tolerance can develop to the subjective effects. A clinical study evaluated the development of tolerance to the effects of around-the-clock oral administration of THC 20 mg every 3.

    The morning THC dose increased intoxication ratings on day 2 but had less effects on days 4 after administration of a cumulative mg dose of THC and 6, while THC lowered blood pressure and increased heart rate over the six-day period suggesting the development of tolerance to the subjective intoxicating effects of THC and the absence of tolerance to its cardiovascular effects.

    Tolerance to the subjective intoxicating effects of THC administered orally was manifested after a total exposure of mg of THC over the course of four days Reference Another clinical study reported that while heavy chronic cannabis smokers demonstrated tolerance to some of the behaviourally-impairing effects of THC, these subjects did not exhibit cross-tolerance to the impairing effects of alcohol, and alcohol potentiated the impairing effects of THC on measures such as divided attention Reference An uncontrolled, open-label extension study of an initial five-week randomized trial of nabiximols in patients with MS and central neuropathic pain reported the absence of pharmacological tolerance measured by a change in the mean daily dosage of nabiximols to cannabinoid-induced analgesia, even after an almost two-year treatment period in a group of select patients Reference Another long-term, open-label extension study of nabiximols in patients with spasticity caused by MS echoed these findings, also reporting the absence of pharmacological tolerance to the anti-spastic effects measured by a change in the mean daily dosage of nabiximols after almost one year of treatment Reference A multi-centre, prospective, cohort, long-term safety study of patients using cannabis as part of their pain management regimen for chronic non-cancer pain reported small and non-significant increases in daily dose over a one-year study period Reference More recently, a double-blind, placebo-controlled, three-way cross-over clinical study with regular cannabis users suggested that tolerance may not develop towards some of the acute effects on neurocognitive functions despite regular cannabis use Reference One hundred and twenty-two subjects who regularly used cannabis average duration of use: Acute administration of vapourized cannabis impaired performance across a wide range of neurocognitive domains: Frequency of cannabis use correlated significantly with change in subjective intoxication following cannabis administration and also correlated and interacted with changes in psychomotor performance meaning that subjective intoxication and psychomotor impairment following cannabis exposure decreased with increasing frequency of use, however the baseline for subjective intoxication and psychomotor impairment was already higher for frequent users compared to less frequent users likely owing to already elevated THC body burden which can cause sufficient levels of intoxication and mild psychomotor impairment.

    The authors suggest that the neurocognitive functions of daily or near daily cannabis users can be substantially impaired from repeated cannabis use, during and beyond the initial phase of intoxication. Pharmacokinetic tolerance including changes in absorption, distribution, biotransformation and excretion has also been documented to occur with repeated cannabinoid administration, but apparently occurs to a lesser degree than pharmacodynamic tolerance Reference Dependence can be divided into two independent, but in certain situations interrelated concepts: The ECS has been implicated in the acquisition and maintenance of drug taking behaviour, and in various physiological and behavioural processes associated with psychological dependence or addiction Reference 2.

    In the former DSM-IV diagnostic and statistical manual of mental disorders fourth edition , the term 'dependence' was closely related to the concept of addiction which may or may not include physical dependence, and is characterized by use despite harm, and loss of control over use Reference There is evidence that cannabis dependence physical and psychological occurs, especially with chronic, heavy use Reference Reference Reference In the new DSM-5, the term "cannabis dependence" has been replaced with the concept of a "cannabis use disorder" CUD which can range in intensity from mild to moderate to severe with severity based on the number of symptom criteria endorsed Reference For a list of symptoms, please refer to the DSM-5 Reference Risk factors for transition from use to dependence have been identified and include being young, male, poor, having a low level of educational attainment, urban residence, early substance use onset, use of another psychoactive substance, and co-occurrence of a psychiatric disorder Reference Notably, the transition to cannabis dependence occurs considerably more quickly than the transition to nicotine or alcohol dependence Reference These increases in both month and lifetime prevalence are thought to be driven by increases in the prevalence of cannabis users.

    Higher frequency of cannabis use was associated with greater risk of disorder incidence and prevalence, supporting a dose-response association between cannabis use and risk of substance use disorders.

    Another study using the U. Survey respondents with month CUD differed significantly from others on all disability components of the survey, with disability increasing significantly, as cannabis disorder severity increased.

    Comparing data between the NESARC - Wave 1 and - Wave 2 , one study reported that the prevalence of cannabis use more than doubled between the two waves of the survey Reference Furthermore, there was a large increase in CUD during this intervening time, with nearly 3 out of 10 cannabis users reporting a CUD in - A retrospective study among a nationally representative sample of 6 Australian adults examining the initiation of cannabis use and transition to CUD found that the mean time from first use to the onset of CUD was 3.

    Younger age of initiation and other substance use were strong predictors of the transition from use to CUD. Social phobia and panic disorder were also associated with transition from cannabis use to CUD. Male cannabis users had greater risk of CUD than female users, but among women, those with depression were more likely to develop a CUD. Early-onset of alcohol and daily cigarette smoking were each associated with marked increased risk of early initiation of cannabis use.

    A handful of clinical studies have examined the differences between men and women with respect to development of dependence, withdrawal symptoms and relapse Reference Physical dependence is most often manifested in the appearance of withdrawal symptoms when use is abruptly halted or discontinued.

    Withdrawal symptoms associated with cessation of cannabis use oral or smoked appear within the first one to two days following discontinuation; peak effects typically occur between days 2 and 6 and most symptoms resolve within one to two weeks Reference - Reference Other symptoms appear to include depressed mood, chills, stomach pain, shakiness and sweating Reference Reference Reference Reference Cannabis withdrawal symptoms appear to be moderately inheritable with both genetic and environmental factors at play Reference There are also emerging reports of increased physical dependence with highly potent cannabis extracts e.

    There are no approved pharmacotherapies for managing cannabis withdrawal symptoms Reference A range of medications have been explored including antidepressants e.

    Zolpidem has also been explored as a potential pharmacotherapy to specifically target abstinence-induced disruptions in sleep Reference Reference However, agonist substitution therapy e. Self-titrated doses were lower and showed limited efficacy compared to high fixed doses and subjects typically reported significantly lower ratings of "high" and shorter duration of "high" with nabiximols and placebo compared to smoking cannabis. A randomized, double-blind, placebo-controlled, six-day, inpatient clinical study of nabiximols as an agonist replacement therapy for cannabis withdrawal symptoms reported that nabiximols treatment attenuated cannabis withdrawal symptoms and improved patient retention in treatment Reference However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use at follow-up.

    Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal symptoms relative to placebo including effects on irritability, depression and craving as well as a more limited effect on sleep disturbance, anxiety, appetite loss, physical symptoms and restlessness. A placebo-controlled, within-subject, clinical study demonstrated that nabilone 6 - 8 mg daily decreased cannabis withdrawal symptoms including abstinence-related irritability and disruptions in sleep and food intake in daily, non-treatment seeking cannabis smokers Reference It also decreased cannabis self-administration during abstinence in a laboratory model of relapse.

    While nabilone did not engender subjective ratings associated with abuse liability i. A follow-up study found that nabilone 3 mg, b. A double-blind, placebo-controlled, week clinical trial testing lofexidine and dronabinol for the treatment of CUD reported no significant beneficial effect compared to placebo for promoting abstinence, reducing withdrawal symptoms, or retaining individuals in treatment Reference in contrast to a previous study that showed efficacy of 40 mg dronabinol daily vs.

    A recent systematic review of the evidence of CBD as an intervention for addictive behaviours reported that to date, only 14 studies have been conducted, the majority in animals with only a handful in humans Reference The limited number of pre-clinical studies carried out to date suggest that CBD may have therapeutic potential for the treatment of opioid, cocaine and psychostimulant addiction, and some preliminary data suggest CBD may also be beneficial in cannabis and tobacco addiction in humans Reference The limited number of pre-clinical studies published thus far suggest CBD may have an impact on the intoxication and relapse phase of opioid addiction, while CBD does not appear to have an impact on the rewarding effects of stimulants e.

    With respect to cannabis dependence, pre-clinical studies show that CBD is not reinforcing on its own, but its impact on cannabis-related dependence behaviour remains unclear Reference In one clinical study, a 19 year-old female with cannabis dependence exhibiting cannabis withdrawal symptoms upon cannabis cessation was administered up to mg of CBD range: In another human study, cannabis with a higher CBD to THC ratio was associated with lower ratings of pleasantness for drug stimuli explicit "liking" , but no group difference in "craving" or "stoned" ratings was noted Reference Reference However, a multi-site, double-blind, placebo-controlled study demonstrated that CBD - mg had no effect on subjective ratings associated with cannabis abuse liability Reference A randomized, double-blind, crossover clinical study in 10 healthy volunteers examining the effects of CBD on the intoxication phase of alcohol addiction reported no differences in feelings of "drunk", "drugged", or "bad" between the alcohol only and the alcohol and CBD groups Reference Reference No pre-clinical studies exist on the use of CBD for hallucinogen-, sedative-, tobacco-, or alcohol-addictive behaviours and no human studies exist on the use of CBD for opioid-, psychostimulant-, hallucinogen-, or sedative-addictive behaviours Reference The ECS is present in early development, is critical for neurodevelopment and maintains expression in the brain throughout life Reference Furthermore, the ECS undergoes dynamic changes during adolescence with significant fluctuations in both the levels and locations of the CB 1 receptor in the brain as well as changes in the levels of the endocannabinoids 2-AG and anandamide Reference The dynamic changes occurring in the ECS during adolescence also overlap with a significant period of neuronal plasticity that includes neuronal proliferation, rewiring and synaptogenesis, and dendritic pruning and myelination that occurs at the same time Reference This period of significant neuroplasticity does not appear to be complete until at least the age of 25 Reference Thus, this neurodevelopmental time window is critical for ensuring proper neurobehavioural and cognitive development and is also influenced by external stimuli, both positive and negative e.

    Based on the available scientific evidence, youths are more susceptible to the adverse effects associated with cannabis use, especially chronic use Reference Reference Studies examining non-medical use of cannabis strongly suggest early onset i.

    Based on the current available evidence, it is unclear for how long some or all of the neurocognitive effects persist following cessation of use. Some investigators have found certain cognitive deficits to persist for up to one year or longer after cannabis cessation, while others have demonstrated a far shorter period of recovery i.

    Though the data from human studies do not establish causality solely from cannabis use, the pre-clinical studies in animals do indicate that adolescent exposure to cannabinoids can catalyze molecular processes leading to functional deficits in adulthood - deficits that are not found following adult exposure to cannabis.

    The authors note that definitive conclusions cannot be made yet as to whether cannabis use - on its own - negatively impacts the adolescent brain, and future research can help elucidate this relationship by integrating assessments of molecular, structural, and behavioral outcomes Reference Factors that may influence persistence of cognitive deficits can include age at onset of use, frequency and duration of use, co-morbidities, and use of other drugs tobacco, alcohol, and other psychoactive drugs.

    While adverse effects associated with THC-predominant cannabis use in youth have been well documented, far less is known about the adverse effects associated with CBD-predominant cannabis use. Nevertheless, as mentioned above, the ECS plays important roles in nervous system development in utero as well as during youth see Section 7. There is evidence to suggest that like the changes seen with the ECS during development and adolescence, there are changes in the ECS associated with ageing.

    In addition, the coupling of CB 1 receptors to G proteins is also reduced in specific brain areas in older animals Reference Age-related changes in the expression of components of the ECS appear similar in rodents and humans Reference Disruption of CB receptors appears to enhance age-related decline of a number of tissues suggesting an important role for the ECS in the control of the ageing process Reference In general, the elderly may be more sensitive to the effects of drugs acting on the CNS Reference A number of physiological factors may lie at the root of this increased sensitivity such as: There is very little information available on the effects of cannabis and cannabinoids in geriatric populations and based on current levels of evidence, no firm conclusions can be made with regard to the safety or efficacy of cannabinoid-based drugs in elderly patients but see below for one of the few clinical studies of safety carried out specifically in geriatric populations Reference Reference Reference Furthermore, as cannabinoids are lipophilic, they may tend to accumulate to a greater extent in elderly individuals since such individuals are more likely to have an increase in adipose tissue, a decrease in lean body mass and total body water, and an increase in the volume of distribution of lipophilic drugs Reference Lastly, age-related changes in hepatic function such as a decrease in hepatic blood flow and slower hepatic metabolism can slow the elimination of lipophilic drugs and increase the likelihood of adverse effects Reference A randomized, double-blind, placebo-controlled, cross-over clinical trial that evaluated the pharmacokinetics of THC in 10 older patients with dementia mean age 77 years over a week period reported that the median time to reach maximal concentration in the blood T max was between 1 and 2 h with THC pharmacokinetics increasing linearly with increasing dose but with wide inter-individual variation Reference Only one clinical study has thus far been carried out looking specifically at the safety of THC in an elderly population.

    In this study, 12 adults aged 65 and older who were deemed to be healthy were included, and exclusion criteria included high falls risk, regular cannabis use, history of sensitivity to cannabis, drug and alcohol abuse, compromised cardiopulmonary function, and psychiatric comorbidities.

    The most commonly reported health problems were hypertension and hypercholesterolemia and subjects reported using an average of 2 medications e. Adverse events first occurred within 20 min of dosing, with all adverse events occurring between 55 and min after dosing and resolving completely within 3. No moderate or serious adverse events were reported in this trial.

    While this clinical study adds important information regarding the safety and tolerability of THC in a healthy elderly population, additional studies are needed to evaluate the safety and tolerability of cannabis and cannabinoids in elderly populations having various co-morbidities.

    In humans, sex-dependent differences have been often observed in the biological and behavioural effects of substances of abuse, including cannabis Reference In male animals, higher densities of CB 1 receptors have been observed in almost all cerebral regions analyzed whereas in females a more efficient coupling of the CB 1 receptor to downstream G-protein signaling has been observed Reference In humans, sex differences in CB 1 receptor density have also been reported, with men having higher receptor density compared to women Reference Sex-dependent differences have also been noted with respect to cannabinoid metabolism.

    Pre-clinical studies in females report increased metabolism of THC to hydroxy-THC compared to males where THC was also biotransformed to at least three different, less active metabolites Reference There is also evidence to suggest that effects of cannabinoids vary as a function of fluctuations in reproductive hormones Reference Reference Together, these findings suggest that the neurobiological mechanism underlying the sex-dependent effects of cannabinoids may arise from sexual dimorphism in the ECS and THC metabolism, but also from the effects of fluctuations in hormone levels on the ECS Reference Reference There is also evidence to suggest sex-dependent differences in subjective effects and development of dependence, withdrawal symptoms, relapse and incidence of mood disorders.

    Data combined from four double-blind, within-subject studies measuring the effects of smoked "active" cannabis 3. These findings suggest that, at least among near-daily cannabis users, women may be more sensitive to the subjective effects of cannabis, especially effects related to cannabis abuse liability compared to men.

    Another study demonstrated dose-dependent sex differences in subjective responses to orally administered THC Reference In this study, women showed greater subjective effects at the lowest dose 5 mg , whereas men showed greater subjective responses at the highest 15 mg dose. Together, these studies suggest that while women may be more sensitive to the subjective effects of THC at lower doses, they may develop tolerance to these effects at higher doses, which could, for example, have implications for the development of dependence.

    For example, while cannabis use among men is more prevalent and men appear to be more likely than women to become dependent on cannabis, women tend to have shorter intervals between the onset of use and regular use or development of dependence commonly referred to as the "telescoping effect" Reference In addition, women abstaining from cannabis use reported more withdrawal symptoms, with some being more severe, than those seen in men and which have been linked to relapse Reference Reference Women with CUD also present with higher rates of certain comorbid health problems such as mood and anxiety disorders Reference Reference Reference The College of Family Physicians of Canada, along with other provincial medical regulatory colleges, has issued a guidance document in for authorizing the use of cannabis for medical purposes.

    Please consult these and any other official guidance documents, as applicable, for additional information regarding dosing and other matters associated with authorizing cannabis for medical purposes. Cannabis has many variables that do not fit well with the typical medical model for drug prescribing Reference While precise dosages have not been established, some "rough" dosing guidelines for smoked or vapourized cannabis have been published see below.

    Besides smoking and vapourization, cannabis is known to be consumed in baked goods such as cookies or brownies, or drunk as teas or infusions. However, absorption of these products by the oral route is slow and erratic, varies with the ingested matrix e. Other forms of preparation reported in the lay literature include cannabis-based butters, candies, edibles, oils, compresses, creams, ointments, and tinctures Reference 80 Reference - Reference but again, limited dosing information exists here with much of the information being anecdotal in nature.

    Dosing remains highly individualized and relies largely on titration Reference Patients with no prior experience with cannabis and initiating cannabis therapy for the first time are cautioned to begin at the very lowest dose and to stop therapy if unacceptable or undesirable side effects occur.

    Subsequent dose escalation should be done slowly, once experience with the subjective effects is fully appreciated, to effect or tolerability. If intolerable adverse effects appear without significant benefit, dosing should be tapered and stopped. Tapering guidelines have not been published, but the existence of a withdrawal syndrome see Section 2.

    Clinical studies of cannabis and cannabis-based products for therapeutic purposes are limited to studies carried out with dried cannabis that was smoked or vapourized and with synthetic or natural cannabis-based products that have received market authorization i. As such, providing precise dosing guidelines for such products is not possible although existing sources of information can be used as a reference point see below. Naturally, dosing will vary according to the underlying disorder and the many other variables mentioned above.

    Average daily dose of dronabinol is 20 mg and maximal recommended daily dose is 40 mg Reference Doses less than 1 mg of THC per dosing session may further avoid incidence and risks of adverse effects.

    Various surveys published in the peer-reviewed literature have suggested that the majority of people using smoked or orally ingested cannabis for medical purposes reported using between 10 and 20 g of cannabis per week or approximately 1 to 3 g of cannabis per day Reference Reference Reference An international, web-based, cross-sectional survey examining patients' experiences with different methods of cannabis intake reported that from among a group of self-selected participants, from 31 countries, the vast majority preferred inhalation over other means of administration e.

    Mean daily doses with smoked or vapourized cannabis were 3. Information regarding cannabinoid potencies of cannabis products i. Daily frequency of use for smoking was six times per day, whereas with vapourizing it was five times per day. First onset of effects for smoking were noted on average around 7 min after start of smoking, 6.

    Other data suggests that those patients who use cannabis for medical purposes use up to one gram or less per day. For example, data from the Netherlands suggests the average daily dose of dried cannabis for medical purposes stood at 0.

    Canadian market data collected from licensed producers under the Access to Cannabis for Medical Purposes Regulations ACMPRs showed that, from April to March , clients had been authorized by their healthcare practitioners to use, monthly, an average of 2. However, since this data is collected per licensed producer, it does not include cases where clients split their authorization into two or more authorizations in order to register with more than one licensed producer at a time or personal production registrations with Health Canada Reference To fulfill orders for oils, licensed producers equate oil to dried cannabis based on the formulation of their oil products.

    On average, licensed producers equate 1 g of dried cannabis to 6. Using this average conversion factor, healthcare practitioners have authorized an equivalent average of Satisfaction ratings for criteria such as onset of effects and ease of dose finding were reported to be higher for smoking and vapourizing i. However, prescription cannabinoid medications e.

    Satisfaction ratings in terms of side-effects were higher for non-prescription unregulated cannabis products, with the inhaled route rated best, although the survey did not ask specific questions about the types of side effects. Satisfaction ratings were only slightly higher for orally ingested cannabis products for criteria such as duration of effects. The majority of survey participants had indicated having used cannabis products prior to onset of their medical condition.

    A prospective, open-label, longitudinal study of patients with treatment resistant chronic pain reported that patients titrate their cannabis dose starting with one puff or one drop of cannabis oil per day, increasing in increments of one puff or one drop of oil per dose, three times per day until satisfactory pain relief was achieved or side effects appeared Reference Mean monthly prescribed amount of cannabis was 43 g or 1.

    Data from randomized, double-blind, placebo-controlled clinical studies of smoked or vapourized cannabis used a daily dose of up to 3. In contrast to the gram amounts of cannabis used with smoked, vapourized, and oral routes of administration, the mean daily amounts for prescription cannabinoids such as dronabinol were 30 mg, for nabilone 4. With respect to the relationship between dosing and psychotropic effects , it has been estimated that an inhaled dose of 0.

    Furthermore, it has been estimated that between one and three puffs of higher potency cannabis would be sufficient to produce significant psychoactive effects Reference One study has shown that while cannabis smokers titrate their dose of THC by inhaling lower volumes of smoke when smoking "strong" joints i.

    For oral administration, a dose of 0. Other provincial bodies may also provide guidelines on monitoring Reference The College of Family Physicians of Canada has recently published a simplified guideline for prescribing medical cannabinoids in primary care Reference The recommendations are as follows:.

    The majority of clinical trials with smoked cannabis for medical purposes have used joints of dried cannabis weighing between and mg. Estimates that are more recent suggest the mean weight of cannabis in a joint is mg Reference In addition, expectation of drug reward can also influence smoking dynamics Reference Little reliable information exists regarding conversion of a "smoked dose" of THC to an equivalent oral dose. It is also important to emphasize that this "conversion factor" appears to relate mostly to psychoactive effects e.

    Further rigorous comparative pharmacology studies are required. In addition, no comparative studies have been done with vaping. In addition, this theoretical conversion factor may or may not apply for therapeutic effects. Indeed, it is important to highlight that two studies reported that individuals using cannabis for therapeutic purposes indicated they used approximately similar gram amounts of cannabis regardless of route of administration Reference Reference A single-dose, open-label, clinical trial of patients with neuropathic pain and using very low doses of inhaled THC reported a statistically significant improvement in neuropathic pain with minimal adverse effects Reference THC administration was associated with a statistically significant reduction in baseline VAS for pain intensity of 3.

    These above-mentioned studies suggest that, at least in the case of chronic neuropathic pain, psychoactive effects can be separated from therapeutic effects and that very low doses of THC may actually be sufficient to produce analgesia while keeping psychoactive effects to a minimum.

    A review of U. Product has been discontinued by the manufacturer post-market; as of February ; not for safety reasons. Newfoundland and Labrador; NS: Prince Edward Island; QC: The pharmacokinetic information described in Section 2. Tea prepared from Cannabis flowering tops and leaves has been documented, but no data are available regarding efficacy Reference On the other hand, to reduce or prevent CINV, a dosage of 5 mg t.

    In either case, the dose should be carefully titrated to avoid the manifestation of adverse effects. The second dose is usually administered 1 to 3 h before chemotherapy. If required, the administration of nabilone can be continued up to 24 h after the chemotherapeutic agent is given. The maximum recommended daily dose is 6 mg in divided doses. Dose adjustment titration may be required in order to attain the desired response, or to improve tolerability.

    More recent clinical trials report starting doses of nabilone of 0. Data from an open-label longitudinal study of cannabis oil for patients with treatment-resistant chronic non-cancer pain reported that patients titrated their cannabis oil dose starting with one drop of cannabis oil per day, increasing in increments of one drop of oil per dose, three times per day, until satisfactory analgesia was achieved or until side effects appeared Reference Maximum daily dose was 5 mg b.

    On subsequent days, the number of sprays can be increased by one spray per day, as needed and tolerated. A fifteen-minute time gap should be allowed between sprays. During the initial titration, sprays should be evenly spread out over the day. If at any time unacceptable adverse reactions such as dizziness or other CNS-type reactions develop, dosing should be suspended or reduced or the dosing schedule changed to increase the time intervals between doses.

    According to the drug product monograph, the average dose of nabiximols is five sprays per day i. The majority of patients appear to require 12 sprays or less; dosage should be adjusted as needed and tolerated.

    Administration of four sprays to healthy volunteers total The Dutch Office of Medicinal Cannabis has published "rough" guidelines on the use of vapourizers Reference Although the amount of cannabis used per day needs to be determined on an individual basis, the initial dosage should be low and may be increased slowly as symptoms indicate. The amount of cannabis to be placed in the vapourizer may vary depending on the type of vapourizer used. The levels of cannabinoids released into the vapour phase increased with the temperature of vapourization Reference Participants inhaled as much of the mg dose of dried cannabis 3.

    In another study, patients followed a similar "cued-puff" procedure and inhaled 4 puffs, followed by an additional round of between 4 and 8 puffs 2 h later for a total of between 8 and 12 puffs over a 2 h period Reference Subjects inhaled 4 puffs at the beginning of the testing session, followed by an additional round of between 4 and 8 puffs 3 h later for a total of between 8 and 12 puffs over a 3 h period. While there are countless anecdotal reports concerning the therapeutic uses of cannabis, clinical studies supporting the safety and efficacy of cannabis for therapeutic purposes in a variety of disorders are limited, but slowly increasing in number.

    Furthermore, the current level of evidence for the safety and efficacy of cannabis for medical purposes does not meet the requirements of the Food and Drugs Act and its Regulations except for those products that have received a notice of compliance and market authorization from Health Canada. It has been repeatedly noted that the psychotropic side effects associated with the use of psychoactive cannabinoids have been found to limit their therapeutic utility Reference 23 Reference 55 Reference 57 Reference Reference A comprehensive review of 72 controlled clinical studies evaluating the therapeutic effects of cannabinoids mainly orally administered THC, nabilone, nabiximols, or an oral extract of cannabis up to the year reported that cannabinoids present an interesting therapeutic potential as anti-emetics, appetite stimulants in debilitating diseases cancer and AIDS , analgesics, and in the treatment of MS, SCIs, Tourette's syndrome TS , epilepsy, and glaucoma Reference However, a more recent systematic review and meta-analysis of randomized clinical trials of cannabinoids i.

    Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete improvement in nausea and vomiting, reduction in pain, a greater average reduction in numerical rating scale pain assessment, and average reduction in the Ashworth spasticity scale Reference There was also an increased risk of short-term adverse events with cannabinoids. Commonly reported adverse events included dizziness, dry mouth, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance and hallucinations Reference Overall, the review and meta-analysis conducted using the Grading of Recommendations, Assessment, Development and Evaluation GRADE approach suggested that there was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic neuropathic or cancer pain as well as MS-associated spasticity, but low-quality evidence to support use for CINV, weight gain in HIV infection, sleep disorders, and TS Reference

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    Dietary supplements containing varying amounts of CBD have been touted as Adams and Alexander R. Todd—Mechoulam's interest was piqued by anecdotal stock, labs, and they were extracting cannabidiol and other cannabis . High- CBD strains of cannabis and other CBD-based products are. CBD oil is made by extracting CBD from the cannabis plant, then Studies have shown that CBD may help reduce chronic pain by and THC in people with cancer-related pain who did not experience High blood pressure is linked to higher risks of a number of health Are There Any Side Effects?. But what evidence do we have regarding cannabis and its effects on sleep? Currently research on the medicinal use of cannabis is restricted due to the legal THC can cause anxiety reactions but higher concentrations of cannabidiol may Certainly anyone who has used alcohol to help sleep knows that in the long run.

    Why Does THC Get You High But Not CBD?



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    Karovka777

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    trupovod

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