DrukQs Smoking & Helminths PDF

DrukQs Smoking Prevalence (2000) Africa – 29% Men – 4% Women United States – 35% Men – 22% Women Europe – 46% Men – 26% Women Western Pacific – 60% Men – 8% Women Smoking (tobacco) Highly addictive Single greatest cause of preventable death globally Leads commonly to diseases affecting the heart, li...

DrukQs Smoking Prevalence (2000) Africa – 29% Men – 4% Women United States – 35% Men – 22% Women Europe – 46% Men – 26% Women Western Pacific – 60% Men – 8% Women Smoking (tobacco) Highly addictive Single greatest cause of preventable death globally Leads commonly to diseases affecting the heart, liver, and lungs Major risk factor for – Heart attacks, strokes, chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), and cancer Also causes peripheral vascular disease and hypertension Cannabis Subjective change in perception and mood Short-term physical and neurological effects – Increased heart rate, increased appetite and consumption of food, lowered blood pressure – Impairment of short-term and working memory, psychomotor coordination, and concentration You guys know all about this stuff… Why?! Why do we smoke? – Hint: it’s not ‘cause “it feels good” Proximate causes are well-known – Question is why does it feel good? Why do we have an affinity for drug use in light of all the associated costs? Chemoprophylaxis and Chemotherapy Hypotheses Plants have evolved an enormous variety of toxins to deter herbivores… … in turn, herbivores have co-evolved to use plant toxins to defend against their own parasites – Known as self-medication, zoopharmocagnosy, or pharmacophagy Chemoprophylaxis and Chemotherapy Hypotheses Woolly bear caterpillars (Grammia incorrupta) – Ingest pyrrolizidine alkaloids to protect themselves from tachinid flies Tobacco hornworm (Manduca sexta) – Co-opt ingested nicotine to defend against the wolf spider and the endoparaitoid, Cotesia congregata Chemoprophylaxis and Chemotherapy Hypotheses Tobacco hornworm (Manduca sexta) Chemoprophylaxis and Chemotherapy Hypotheses Urban sparrows and finches – Place cigarette butts containing residual nicotine in nests to defend against nestdwelling ectoparasites such as mites Helminths Helminths – parasitic worms (e.g. hookworm, pinworm, etc. Chemoprophylaxis and Chemotherapy Hypotheses Some species ingest plant toxins to specifically defend against helminths (parasitic worms) – Domesticated Lambs Respond to gastrointestinal parasite infections by increasing their intake of alfalfa tannins – Wild chimpanzees Ingest Aspilia and the bitter pith of Vernonia amygdalina to treat intestinal helminth infections Chemoprophylaxis and Chemotherapy Hypotheses Ethnomedicine – The deliberate use of plants for medicinal purposes in humans Increasing evidence that the plants that are incorporated into many diets provide protection against parasites Billing and Sherman (1998) – Argue that the addition of spices to food functions to defend against meat-borne pathogens Chemoprophylaxis and Chemotherapy Hypotheses So, what are you saying, Ian? – It is possible that “recreational” drug use in humans can be explained by the antiparasitic properties of these plant compounds Chemoprophylaxis and Chemotherapy Hypotheses Three of the worlds most popular recreational drugs are effective treatments against helminthes – Nicotine (the psychoactive component of tobacco) and arecoline (the psychoactive component of betel-nut) Both have been used as commercial anthelmintics in animals – Cannibus Toxic to plant-parasitic nematodes Chemoprophylaxis and Chemotherapy Hypotheses Hypothesis: – Human recreational drug use might involve neuropsychological mechanisms that evolved to regulate the intake of plant neurotoxins Function to prevent or reduce infection of helminthes and other macroparasites – This hypothesis does NOT require conscious awareness of these mechanisms Chemoprophylaxis and Chemotherapy Hypotheses Two pharmacophagy hypotheses for the human use of psychoactive plant toxins – Both are based on plants natural defenses – First Even when they are not under attack, plants maintain a basal level of plant toxins to deter attacks This is a form of chemopraphylaxis known as a constitutive defense – Second When they detect an herbivore attack, plants – Up-regulate energetically expensive toxin production When the attack ceases, plants – Down-regulate expensive toxin production This is a form of chemotherapy (in its non-cancer specific sense) Known as inducible defense Chemoprophylaxis and Chemotherapy Hypotheses Chemoprophylaxis hypothesis – The human propensity to consume neurotoxic plants prevents or limits infection by helminths Chemotherapy hypothesis – Consumption of psychoactive substances should be Up-regulated by infection serving to limit infection levels Down-regulated if and when the infection is cleared Nicotine as a Model Drug Why might we surmise that nicotine might serve as an anthelmintic in humans? – Modern anthelmintic such as levamisole and tetrahydropyrimidines achieve their effects by targeting the same receptors as nicotine Nicotinic acetylcholine receptors (nAChRs) on somatic muscle cells Induces spastic paralysis of the parasite, leading to its expulsion Nicotine as a Model Drug Why might we surmise that nicotine might serve as an anthelmintic in humans? – Nicotine is an extremely potent neurotoxin and the quantities absorbed via smoking and chewing are surprisingly high Nausea and vomiting are induced by doses of 2-5 mg The lethal dose for an adult human is 30-60 mg Smokers typically absorb – 1-2 mg per cigarette – 4.5 mg per “wad” – Thus, tobacco users are absorbing quantities of nicotine just below that which induces acute toxic response Nicotine as a Model Drug Why might we surmise that nicotine might serve as an anthelmintic in humans? – One billion adults are tobacco users These billion smoke about 15 billion cigarettes per day – Approximately one billion people in developing regions of sub-Saharan Africa, Asia, and the Americans are infected with one or more helminths Tobacco use vs. Helminths Roulette et al. (2014) – Experimentally studied nicotine use and prevalence of helminthiasis in the Aka of the Central African Republic (CAR) – Findings Worm burden was inversely correlated with nicotine exposure from tobacco use – Evidence of chemotherapy hypothesis Treating helminth infection with a commercial anthelmintic reduced smoking – Evidence of down-regulation of drug intake Among individuals whose helminth infections were treated with commercial anthelmintics, higher smoking levels limited reinfection with helminthes – Evidence of chemoprophylaxis hypothesis