Benzodiazepine therapy can give rise to physiologic and psychologic dependence based on the drug's dosage, duration of therapy and potency. 1 Thus, dependence will develop sooner (such as in one to two months) in a patient who is taking a high dosage of a high-potency agent such as alprazolam than in a patient who is receiving a relatively low dosage of a long-acting, low-potency agent such as chlordiazepoxide. As a result of physiologic dependence, withdrawal symptoms emerge with rapid dose reduction or abrupt discontinuation of the drug.
And, exacerbating these two age-related erosive events, some catabolites
of tryptophan can lead to the formation of mutagenic nitrosamines or
the activation of an immunosuppressive receptor (which is usually
triggered by toxicants such as xenobiotics), promoting carcinogenesis
(Mezrich, et al., 2010; Chung & Gadupudi, 2011).
The consumption of a supplement of tryptophan will likely nurture or augment these disastrous age-associated disease states, by raising injurious tryptophan derivatives (particularly in the presence of a vitamin B6 deficiency, an insufficiency of stomach acid, a magnesium deficit, and a vitamin B3 deficiency).
Furthermore, tryptophan side effects in regards to greater mortality were shown in animal experiments (., Catrina, et al., 2001) using melatonin, whereas the study authors cautioned:
“[...] melatonin had a deleterious effect on the survival rate raising the question whether it is correct to assume that the hormone shows lack of adverse reactions.” [emphasis added]
In regard to serotonin's involvement in the promotion of higher mortality, one of its anti-longevity effects is conceivably the reabsorption of phosphate (a pro-inflammatory chemical) by the kidneys since klotho, an anti-aging protein, facilitates the excretion of phosphate from the kidneys (Peat, Nov. 2012).
Since tryptophan, serotonin, and melatonin meddle with basic energy production in cells, and since metabolic efficiency and functionality decreases proportionally with aging (Fannin, et al., 1999; O'Toole, et al., 2010) due to various factors, it seems coherent in biological terms that these substances are less prevalent, thus less “essential” or needed, in older people, as a further decrease of an already suboptimal general metabolic working order will aggravate physiological function systematically, increase the risk for disease (as exemplified and foreshadowed with tryptophan side effects), promote the aging process, and explains the increased mortality related to the administration of these substances.
Several tryptophan side effects, such as tryptophan's carcinogenic activities, the deterioration of metabolic energy function, and the promotion of hypertension, can rather readily account for a greater death rate.
Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.