Screenshot of the NRC Isotopic Enrichment Calculator (v.1.81) as applied to the positive ionization electrospray mass spectrum for [d-Asp3]MC-RR (1) grown in a medium having 98% of nitrogen as nitrogen-15. Data input is in the left panel with output on the right-hand panel including the isotopic abundance with the best fit to the observed m/z and intensities, together with a representation of the mass spectrum (circles: observed m/z and intensities, vertical bars: calculated values given the molecular formula, charge-state, and isotopic composition of nitrogen).
Mass Spec Calculator Professional 4.09
In general, the elderly may be more sensitive to the effects of drugs acting on the CNSReference 557. A number of physiological factors may lie at the root of this increased sensitivity such as: (1) age-related changes in brain volume and number of neurons as well as alterations in neurotransmitter sensitivity which can all increase the pharmacological effects of a drug; (2) age-related changes in the pre- and post-synaptic levels of certain neurotransmitter receptors; (3) age-related changes in the sensitivity of receptors to neurotransmitters; and (4) changes in drug disposition in the elderly being generally associated with higher concentrations of psychotropic drugs in the CNS. 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 421Reference 557Reference 558. 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 drugsReference 557. 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 effectsReference 557.
Lastly, a four-week, prospective, double-blind, randomized, cross-over clinical study of 5 mg daily doses of dronabinol in 24 adult women with severe, chronic anorexia nervosa reported a small, yet significant increase in body mass index (BMI) compared to placeboReference 322.
Determine if the patient has persisting neuropathic pain. Screening criteria for persisting neuropathic pain include daily or almost daily pain with typical neuropathic characteristics; a duration of at least three months; and an impact on the patient's quality of life. If the patient does not meet the screening criteria for persisting neuropathic pain, conduct another evaluation and make a referral to another healthcare professional. If the patient does meet the screening criteria for persisting neuropathic pain, determine if the patient has tried standard medications. If no, try standard medications. (Note a: Standard medications include antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs). If yes, determine if they have/had a good response to standard medications. (Note b: At least 30% reduction in pain intensity). If yes, continue standard medications. If no, determine if the patient is willing to consider cannabinoids or cannabis. (Note c: Consider past experience with cannabis or cannabinoids, potential for side effects or history of side effects, willingness to smoke/vaporize/ingest orally). If no, consider continuing standard medications. If yes, determine if there is a risk of substance abuse and psychiatric or mood disorders. (Note d: Determine substance abuse history; history of psychiatric or mood disorders. If yes or at high risk for substance abuse, proceed with caution and close observation (see Sections 2.4, 5.0, and 6.0); coordinate with substance abuse treatment programs. If there is a history or risk of psychiatric disease (schizophrenia) or bipolar disorder see Section 7.7.3 and consult with a psychiatric specialist before proceeding). If yes, coordinate with the proper substance abuse or psychiatric resource to determine if the risk/benefit is favourable with coordinated care. If it is not favourable, the patient is not a candidate for cannabinoids or cannabis. If it is favourable or if there is no risk of substance abuse and psychiatric or mood disorders, determine if the patient is cannabis or cannabinoid naïve. If no, obtain a full history of previous cannabinoid use. (Note e: Specific cannabinoid, dose, route of administration; symptoms treated and outcome; adverse effects). If the patient is cannabis or cannabinoid naïve or once the full history of previous cannabinoid use from a non-naïve patient has been obtained, try an oral cannabinoid by prescription, such as nabilone or nabiximols buccal spray. If the trial with the prescription oral cannabinoid fails or if it is not financially feasible, consider cannabis. (Note f: Discuss the fact that there are not yet clear guidelines regarding efficacy, doses and toxicity; raise awareness of oral and vaporized routes of cannabis administration; refer patient to Health Canada website and documents regarding access to cannabis product(s); follow the usual clinical guideline to start low and titrate dose slowly). Cannabis can be administered orally, by smoking or by vaporization. It is important to educate the patient regarding the risks, benefits, side effects and non-diversion of cannabis. Finally, monitor the patient to determine efficacy, side effects and diversion of cannabis and adjust treatment accordingly. (Note g: Efficacy should aim for at least 30% decrease in pain intensity).
The contraindications that apply to those considering using prescription cannabinoid-based therapies (such as nabilone (e.g. Cesamet), nabiximols (e.g. Sativex) or dronabinol (e.g. Marinol, no longer available in Canada)) also apply to those considering using cannabis, especially THC-predominant cannabis. Healthcare professionals may also wish to consult the College of Family Physicians of Canada preliminary guidance document on authorizing dried cannabis for medical purposesReference 586 and the recent simplified guideline for prescribing medical cannabinoids in primary careReference 587. 2ff7e9595c
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