Nicotine and CBD
Smoking and Nicotine
Nicotine is a synthetic chemical that contains nitrogen, which is produced by numerous types of plants, including the tobacco plant. When tobacco is smoked, nicotine activates the release of dopamine, the “happy” chemical in the brain. The hormone dopamine is a neurotransmitter that impacts the pleasure areas of the brain. Research also shows that nicotine may improve memory and concentration.
Unfortunately, the nicotine in tobacco is an integral part of cigarette addiction. Someone who is addicted to the nicotine in tobacco continually craves nicotine to release the gratifying dopamine. As the addiction to smoking tobacco grows, so does the amount of nicotine required to stimulate and relish the sensations of dopamine. Once someone stops smoking, one’s nicotine levels drop immediately. This sudden decline in nicotine levels may cause withdrawal symptoms such as craving tobacco, anxiety, irritability, headache, weight increase, and difficulty concentrating. The side effects of nicotine can also affect the heart, hormones, and gastrointestinal system.
Nicotine is neither cancer-causing, nor is it extremely harmful on its own. The real culprits that cause serious illness and death from cancer, lung, and heart disease are the tar and lethal gases that are released from burning tobacco when one smokes. However, nicotine could be seriously addictive and exposes people to the severe ramifications of tobacco dependency. Smoking is the top preventable cause of death in the United States, and there are over one billion tobacco smokers worldwide. Chewing or snorting tobacco products releases more nicotine into the body than smoking.
Nicotine Replacement Therapy (NRT)
Most smokers agree that quitting smoking for the first time often results in failure and misery. Nicotine replacement therapy (NRT) is a process that provides an opportunity for smokers who are highly dependent on nicotine to cease their smoking habit. NRT helps smokers give up smoking without eliminating the nicotine from their body. Nicotine replacement products help manage withdrawal symptoms by gradually decreasing one’s nicotine intake. Over time, the smoker’s dependence on nicotine would substantially diminish, and the craving for nicotine would be curbed.
The NRT product that one chooses depends on his or her preferred way to take in nicotine. A smoker may choose to wear a discreet nicotine patch, suck on a nicotine lozenge, or chew nicotine gum.
The nicotine patch delivers nicotine through one’s skin to help reduce withdrawal symptoms related to smoking, including cigarette cravings. Invented in 1984 by doctors at UCLA, nicotine patch was the first popular transdermal medication and has aided millions of smokers to give up cigarettes. The patch is convenient and straightforward to use. The user puts it on upon waking up in the morning and then lets the patch do its job. One should start this medication on his or her first day of quitting smoking. Apply the patch to a dry and clean non-hairy area on one’s trunk or upper arm.
The nicotine lozenge is candy-like, sugar-free tablet that comes in various flavors like cinnamon, fruit, and mint. Place the nicotine lozenge in the mouth and allow it to dissolve in 20 to 30 minutes. The nicotine is then delivered into the bloodstream, relieving the urge to smoke. Lozenges should only be used as needed. However, since they are similar to candy, the potential to abuse this NRT is significant.
The nicotine gum is one of the most inexpensive NRT products. However, it is slower at delivering nicotine than most NRT products. It is essential to rest the gum in one’s cheek, but some people do not like the peppery taste of the gum. Also, what one eats or drinks affects how his or her body absorbs the nicotine from the gum. It is best to refrain from acidic substances like coffee, soft drinks, and juices for about 15 minutes before and during gum use.
Vaping and The Toxicity of E-Liquids
Fortunately, nicotine vape juice helps reduce the toxicity of conventional cigarettes. Fewer ingredients in nicotine vape juice indicate more pleasure with fewer health issues. However, be forewarned that nicotine vape juice is not entirely safe. Excessive nicotine may still result in behavioral and psychological disorders, sleeping problems, and elevated blood pressure leading to heart disease.
With a sudden decrease in tobacco use in cigarettes, a flourishing new market for the e-cigarette business emerged, along with the flavored liquids that are vaporized and inhaled. The popularity of e-cigarettes also prompted many people to be concerned about whether vape pens and e-liquids are safe to use.
E-liquids contain various levels of nicotine and other chemicals, including propylene glycol and vegetable glycerin, called PGVG. Those substances are considered non-toxic if taken orally, but they can be dangerous if heated and inhaled.
The University of North Carolina (UNC) research team set up a database of the e-liquid ingredients and the results of their ftoxicology tests. Flori Sassano, the study's co-author, together with a research team, established a method to assess 148 different e-liquids quickly. They wanted to find out how the chemicals might affect fast-growing human cells, including those from the lungs and upper airways. Sassano said that swallowing something is not the same as inhaling it. He explained that the PGVG, which is the base for all e-liquids, is fatal by itself when cells come in contact with it, be it in liquid or vapor form.
Sassano also asserts that although the flavors of the e-liquids all sound natural, they are not. These vape juices contain chemicals, which make the vape juices more toxic. The contents of the e-liquids differ extensively. Two flavorings, vanillin, which delivers a vanilla flavor, and cinnamaldehyde, cinnamon flavor, were lethal to cells in the lab. Sassano hopes the system they developed could be used on a broader scale and contribute to the creation of new regulations over their use.
Vaping Products and Respiratory Illnesses
An epidemic of severe respiratory lung injury linked to the use of vaping products has affected over 530 people in the U. S and one U.S. Territory. These illnesses are not infectious but connected to exposure to chemicals from vaping products. Many patients said they used some vaping products containing THC recently. They reported that, at the onset, symptoms include breathing difficulty, shortness of breath, or chest pain before hospitalization. Although these cases seem comparable, it is not evident if they have a common cause, or if they involve different diseases with comparable presentations. The investigation has not determined any specific product or substance or vaping product that is linked to all cases.
Cigarette Users Turned Cannabis Users
Cigarette smoking remains to be the foremost preventable cause of disease and early death in the United States. Considerable drops in smoking occurrence over the past 50 years in the United States were seen, although the percentage of this decline has decreased in recent years. The stunted decline in cigarette use could be, in part, due to the substantial increase in daily cannabis use among smokers.
Due to health hazards associated with nicotine consumption, many smokers are now switching from nicotine to CBD vape juice. The most accelerated rates in the upsurge of cannabis use were among those aged 26 years and older versus those aged 12 to 17 years and 18 to 25 years. However, cigarette smokers aged 12 to 17 were 50 times more likely to become daily cannabis users than young people who do not smoke cigarettes. In 2014, 28 percent of daily cigarette smokers and 13 percent of non-daily cigarette smokers aged 12 to 17 used cannabis daily, which could imply that 40 percent of 12 to 17-year-olds who smoke cigarettes used cannabis every day in 2014.
CBD Oil as E-Liquid
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are two compounds found in the marijuana plant, Cannabis sativa. Both compounds have comparable chemical structures but do not have the same psychoactive effects. CBD does not give the user the "high" associated with THC. CBD, however, provides relief for an extensive range of health issues, from mild anxiety and depression to severe epilepsy and joint pain. The ability to provide relief without the "high" of marijuana makes CBD appealing to people looking for an all-natural remedy to address their health concerns.
CBD products come in many forms that make the consumption of the compound more convenient and accessible. As a sublingual tincture, drops of the compound can be applied sublingually. Massage creams may be applied to the skin safely. CBD may even be directly consumed as is or added to food and beverages.
One of the benefits of CBD extracts is that they are nicotine-free. High-quality CBD oils contain nothing other than cannabinoids and all the natural goodness from the hemp plant. Hemp seed oil comes from the seeds of the marijuana plant. The seeds have a robust profile of nutrients, fatty acids, and beneficial bioactive compounds. Full spectrum hemp oil that also holds plant matter may add other active compounds, which may help with some health issues.
A common side effect of CBD consumption is relief from pain and anxiety. CBD users also report feeling relaxed and experiencing an overall improvement in mood. Higher doses of CBD may induce sleepiness or drowsiness, but in small doses, CBD may promote alertness, as suggested by a study.
CBD oil made from hemp does not contain enough THC to give the user a euphoric high. CBD provides a feeling of comfort and relaxation without the adverse side effects of marijuana. The most frequently experienced effects associated with vaping CBD oil include pain relief, reduced anxiety, improved mood, lethargy (in high doses), and attentiveness (in low doses).
Among the growing number of CBD users, the most preferred CBD product is the CBD vape oil. Vaping CBD is the most cost-efficient and convenient alternative for many smokers and vapers. CBD made for vaping is often referred to as CBD vape oil, although it does not contain any oil. A more suitable term for it is CBD vape juice, CBD e-juice, CBD e-liquid or CBD distillate. CBD for vaping is processed with food-grade ingredients, so it is safe for oral intake.
Millions of cigarette smokers are making the switch to e-cigarettes along with the impressive expansion in vape juice products. Vaping is a popular and straightforward method to consume CBD. According to a study conducted by the Institute for Social Research, marijuana vaping among youth has grown by 58% in a single year. Some people with chronic pain or other medical conditions treated with CBD turn to vaping as it provides convenient and swift relief. Inhalation of cannabinoids has a typical onset of 1-3 minutes with a lasting duration of 1-3 hours.
Vaping is one of the most bioavailable ways to take CBD. Greater bioavailability means the user can absorb more of the drug. Many CBD users experience an almost instantaneous effect when they first vape CBD. CBD edible forms typically take effect after more than 30 minutes. People suffering from chronic pain, seizures, anxiety, and similar ailments do not have that option to wait.
Also, vaping leaves a higher cannabinoid retention rate than smoking does. Having a retention rate from 60% to 90% means there is less waste of valuable cannabinoids from vaping rather than smoking. Compared to smoking raw flower or products with nicotine, vaping CBD may contain less carcinogenic byproducts, which means less toxicity to the vaper.
Basic Elements of Vaping
All vapes have a battery, a heating element (also called an atomizer), a mouthpiece and a chamber to hold the material to be vaped. The heating element vaporizes the material in the chamber, and the user inhales the vapor through the mouthpiece.
Using a CBD vape pen is the most common way to vape CBD. A vape pen is a vaporizer that is shaped like a pen. Vape pens are also called e-cigarettes, e-cigs, e-hookahs, or electronic nicotine delivery systems (ENDS). Some vape pens look like USB flash drives or other everyday items. Some e-cigarettes look very similar to ordinary cigarettes, cigars, or pipes.
CBD vape products come in a small cartridge, and a battery is needed to turn the extract into an inhalable vapor. A battery is also called a vape pen. A vape pen is a battery-powered device that heats the CBD liquid and turns into vapor that one can inhale. There are numerous models of pens, atomizers, and e-cigarettes. There are even tabletop models that plug into the wall. All of these devices work by heating an electric coil. At a specific temperature, the plant extracts heat up enough to turn into vapor. The vapor is inhaled and drawn into the lungs, then exhaled or “puffed out.”
Various vape pens are intended to be used for CBD consumption. Cheaper versions of vape pens tend to have fixed temperatures that are high enough to hit over 350+degrees without combusting. With expensive vape pens, the user can control temperature or voltage.
A vape pen with temperature and voltage control is ideal because cannabinoids activate at different temperatures. THC and CBD can be activated at lower temperatures, while CBG (cannabigerol) and CBN (cannabinol) require high temperatures.
Computing for CBD Dosage
As each vape pen and tank may provide different levels of vapor output, it is difficult to determine how much CBD is in each inhalation. Also, each person’s puffs take in varied amounts of vapor. A standard 1 mL cartridge can provide 100 to 200 puffs in total, depending on the duration of the puff. A 1 mL cartridge containing 200 mg CBD would give the vaper 1 mg to 2 mg of CBD per puff.
Some vape mods have a puff counter that keeps track of every puff that the vaper takes. This feature gives the vaper an idea how many puffs it takes to clear a tank of CBD vape juice. To compute for the dose per puff, divide the total amount of CBD in the tank by the total puffs. Another way to calculate one’s daily intake is to monitor how many times he or she refills the tank. However, one has to determine the total CBD per tank first. If one vaped half of the tank that contains 100 mg CBD, then he or she has vaped 50 mg CBD. If it took that person 200 puffs, that means about 1 mg CBD per puff was inhaled.
One’s dosage may change based on the medical condition being treated. These recommended dosages are for taking CBD orally. Due to the higher bioavailability of vaped CBD, the amount of CBD needed for vaping is significantly reduced. It is always a good idea to start one’s dosage as low as possible. Then, the vaper slowly increases it in 5 mg increments until he or she finds the lowest dosage that works for him or her. These are the recommended dosages for particular health issues:
- Increase appetite in cancer patients – 2.5 mg CBD (best combined with THC at a 1:1 ratio)
- Epilepsy – 200-300 mg CBD
- Chronic pain – 2.5-20 mg CBD
- Social anxiety – 40-300 mg
- Sleep disorders – 40-160 mg CBD
CBD is not currently regulated by the Food and Drug Administration (FDA, and there is no proper dosage of CBD that everyone should take. Different people respond to different doses of CBD. However, most of the human studies suggest dosages between 20 and 1,500 milligrams per day. Finding the right dose of CBD for one’s vaping may be challenging as well. Several factors in determining personal dosage depend on the user’s reason for vaping. Those factors include CBD strength, delivery method, body weight, body chemistry, and severity of health condition. However, according to experiments conducted at King’s College London, CBD users may each have different experiences as cannabidiol acts on multiple molecular pathways in the body,
Each delivery method that a user chooses to consume CBD creates a specific level of bioavailability. Most drug companies recognize that vaping has the highest level of bioavailability. A high level of bioavailability means more CBD content would get absorbed into the bloodstream. Also, CBD vape juice can produce results similar to a CBD capsule, edible, and tincture. Because vaping requires the user to use a minimum amount of CBD, vaping is one of the most efficient methods for cannabidiol consumption. The bioavailability of CBD vape oil is 40-50%, which means for every 10 mg of CBD that one vapes, his or her body can only absorb and utilize 4-5 mg of it. This piece of information is useful when one looks into computing for personal dosage.
CBD and Drug Tests
Many people are concerned about whether or not CBD would show up on a drug test if they vape CBD. The good news is that it would not. However, use only a pure broad-spectrum CBD product which does not have any THC added. Full-spectrum CBD products contain trace amounts of THC, and CBD may be detected during a drug test. To be sure that there would be no trace of THC in the body, choose a THC free product that has "broad spectrum" or "isolate THC free" on the label.
CBD and Nicotine
Both CBD e-liquid and CBD oil are nicotine-free. These products primarily use CBD extracted from the legal and industrial hemp plant. The significant difference is in the liquid that delivers CBD to the body. CBD oil typically uses high-quality and natural oil. CBD e-liquid, on the other hand, uses the natural VG (vegetable glycerin) liquid found in nicotine-based e-liquids.
One vital piece of information to keep in mind is that under no circumstances should anyone combine oil intended for sublingual use with e-liquid. CBD products intended for sublingual or oral consumption use a carrying agent like olive oil, coconut oil, hemp oil, or MCT oil. These oils do not mix with the vegetable glycerin (VG) or propylene glycol (PG) that is found in e-liquids. They may appear to be comparable, but they are very different substances.
Oils are not designed to be heated at high temperatures. However, the VG and PG used in e-liquids have the potential to produce vapor and a ‘throat hit’ that simulates conventional smoking. Mixing the oils with VG or PG would likely damage the vaping device and possibly endanger someone. Also, it is improbable that anyone would want to vape coconut oil.
Mixing CBD and Nicotine
There are several brands of CBD e-liquids that contain a fair amount of nicotine. Although these products are popular in the United States, they are rarely found in the United Kingdom. Specially blended juice that contains both compounds may be advertised as safe to use. However, as nicotine is an addictive substance, vaping with CBD e-liquids that contain nicotine may bring about some unwarranted risks. Purists strongly believe that it is best to vape CBD independent of any nicotine. For people who want to enjoy the full benefits of vaping their CBD e-liquid, keeping CBD clean and green is critical.
Meanwhile, some people prefer to mix CBD and e-liquid. However, most vaping and CBD enthusiasts do not recommend this blend. Diluting CBD e-liquid with a regular e-liquid is not only unnecessary but impractical. Also, It is of utmost importance that one mixes the right products when considering mixing CBD with e-juice. CBD oil and CBD e-liquid are two different products intended for different purposes.
Nicotine is typically an essential ingredient in sophisticated or expensive e-liquids. However, nicotine is not a necessary inclusion. One innovative option that is particularly designed for cannabis and CBD users is zero-nicotine e-liquid, which is an ideal way to thin the vape oil without the potentially undesirable effects of nicotine. Nicotine e-liquids can be extremely beneficial for anyone trying to withdraw from smoking cigarettes. However, using a mid or high-nicotine juice with cannabis or CBD oil is not recommended to someone not accustomed to nicotine. Unfortunately, many cannabis users believe that e-juice companies only sell liquids with nicotine.
CBD vape oil is needed to mix with one’s favorite e-juice. CBD vape oil is used together with a vaporizer that has a refillable e-liquid chamber. One can blend CBD with either nicotine or nicotine-free e-liquid. However, the combination of CBD oil and e-liquid would leave an unpleasant taste in the mouth, as well as clog up coils in the vaporizer. For enhanced flavors, choose a flavored e-liquid or terpene-infused vape oil. Still, for someone who is a beginner at vaping CBD but has not vaped nicotine, there is absolutely no reason to start a nicotine addiction now.
CBD E-Juice and Nicotine Salt
Nicotine salt is a type of nicotine that is found naturally in tobacco leaves. The extra salt content lowers the temperature at which the oils burn. This action is more cost-effective and advantageous to one’s vape pen. However, the nicotine salt may also cause unwarranted side effects such as delivering a stronger dose of nicotine that could get someone addicted quickly. Combining nicotine salt with CBD e-juice induces vapers to inhale more deeply and hold the vapor in longer.
Nicotine salts have a higher nicotine content compared to the traditional freebase nicotine salt found in most e-liquids. Nicotine salt e-liquids have a particular ingredient, benzoic acid, that helps to make nicotine salts as smooth and appetizing in higher strengths.
Still, there is controversy regarding diacetyl, one of the primary ingredients in cheap nicotine salts. Diacetyl is the chemical used to deliver the flavor of e-juice. However, little is known about its long-term effects on human health. For the best CBD vape juice, consumers should be cautious of added flavors. Stay away from synthetic cannabinoids or nicotine salt. These products may contain some of the health benefits of CBD, but the additives used to produce the vape oil are often untested and contain minimum amounts of CBD.
Pre-made e-liquids can be the ideal complement of one’s preferred cannabis or CBD oil and e-cig. However, different e-liquid products contain different ingredients, and the ratio of the ingredients may vary extensively. Even if a vape oil seller is responsible and uses nothing but the finest ingredients for vape juice blends, cannabis and CBD oil producers that concoct vape-ready blends may be sacrificing variety and quality to provide convenience to their patrons.
Pre-made cannabis juice blends are also dependent on propylene glycol or PG. PG is not bad, but it brings about limitations on one’s options. While PG may provide the “throat hit” experience that many vapers and ex-smokers appreciate, it is not an experience that everyone relishes. One of the best options currently available is high vegetable glycerin or VG e-liquid, which delivers a smooth vaping experience. VG is also likely to give off much bigger clouds of vapor, which is not considered a disadvantage by many cannabis enthusiasts.
One would notice the naturally sweet taste of the vegetable glycerin when vaping with a flavorless VG e-liquid. With VG e-liquids, the user may also choose zero nicotine, which is the organic experience that is consistent with cannabis culture. Natural products are also ideal for anyone considering either cannabis or CBD strictly for their medicinal benefits. Blending cannabis or CBD oil with a VG e-liquid also eradicates the possibility of allergies associated with PG. Hence, vapers prefer to use VG-based juices for everyday nicotine-free vaping.
The healing characteristics of CBD make CBD vape juice a healthier option to nicotine or cannabis, which contains THC. People who suffer from specific ailments may try CBD vape juice. CBD oils can easily be infused into e-liquids to create CBD vape juice. One can reap the benefits of CBD oil while enjoying his or her favorite e-liquid flavors.
More Research Needed
It has already been proven that nicotine is one of the most addictive substances available. However, there is no scientific or anecdotal evidence to prove that combining nicotine with CBD makes either substance addictive. Meanwhile, hemp does not have any addictive properties. There has never been a report about people becoming addicted to taking any kind of cannabinoid supplement.
Results from research suggest that people who consistently consume cannabis in large amounts per intake without nicotine may experience a shrinking of the hippocampus, which reduces memory retention. On the other hand, people who take cannabis combined with nicotine are likely to experience an expansion of the hippocampus, which enhances memory. The researchers did not identify any correlations between their findings and a specific cannabinoid compound, however. More research is necessary to validate the results of the investigation.
Replacing Nicotine with CBD
Can CBD replace nicotine? The answer depends on the individual vaper. Discontinuing nicotine use is difficult, even when replaced with CBD. There are a few side effects of vaping without nicotine. Those who are considering to replace their nicotine vape juice with CBD must be well-informed of these effects.
Vape juice comprises of two base liquids, propylene glycol and glycerol, that can cause a painful reaction. These liquids are carcinogenic and cancer-causing when vaporized. Experienced vapers know that heated vape juice can irritate the mouth, throat, and airways when smoked without nicotine.
Nicotine helps reduce the irritation caused by the base ingredients in vape juice. Vape juice without nicotine can prompt an immune system response. Most inflammation associated with nicotine-free vaping occurs in the throat, lungs, and in some cases, white blood cells.
FDA's Final Rule
Close to half a million people in the United States die an early death every year from diseases brought about by smoking cigarettes and being exposed to tobacco smoke. In 2009, the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) amended the Federal Food, Drug, and Cosmetic Act (FD&C Act) to authorize FDA to protect the people from the damaging effects of tobacco use, through science-based tobacco product guidelines.
On May 10, 2016, The U.S. Food and Drug Administration (FDA) issued a final rule (the "deeming rule") to consider other products that meet the legal definition of a "tobacco product," except for accessories, to be under FDA's regulations. Deemed products include ENDS, cigars, pipe tobacco, nicotine gels, water pipe (or hookah) tobacco, and any future tobacco products. The deeming rule and FDA's regulation of these products took effect on August 8, 2016.
Regulatory Requirements for ENDS Products
Once the deeming rule took effect, many of the regulatory and legal necessities that had been implemented for makers of cigarettes, smokeless tobacco, cigarette tobacco, and roll-your-own tobacco since 2009, became applicable to manufacturers of e-cigarettes and other ENDS products. Furthermore, the following regulatory provisions also apply to deemed tobacco products and ENDS products:
- Minimum age requirement and identification requirement to restrict sales to underage youth;
- Requirements to display specific health warnings on labels or packages, and advertisements such as, "WARNING: This product contains nicotine. Nicotine is an addictive chemical" and
- Prevention of selling tobacco products and ENDS products through vending machines, unless the machine is in a facility youths are not admitted.
The U.S. Food and Drug Administration (FDA) and FTC (Federal Trade Commission) also sent warning letters to businesses that make and sell flavored e-liquids for violations. The warnings were in connection to online posts by social media influencers on their behalf. The posts did not have the required nicotine addiction warnings. FDA has been holding retailers and makers of the ENDS products responsible for marketing and sales practices that made e-cigarettes more accessible to the youth.
Nicotine and addiction are two problems that currently plague the worldwide community. Many people hope to resolve these problems by turning to cannabis-derived CBD products. Unfortunately, the reality is that we live in a consumerist culture, and everyone is trying to make a profit off the growing CBD industry. Consumers must be aware that some CBD products are closer to snake oil than they are to natural cannabis-derived CBD oil.
A simple visual test would help one assess the consistency of a CBD product that he or she purchases. If the CBD product for vaping has a thick waxy consistency, then it is safe to use. Otherwise, stay away from CBD products that are too diluted. Not only would these products fail to provide the CBD benefits that many people seek, but these products are most likely to be synthetic. When purchasing CBD products, always consult a doctor or a trained medical professional with any questions. CBD consumers must come together and ensure that big businesses do not mislead people and corrupt the amazing medical properties that CBD has to offer.
More Information on Nicotine
Nicotine is a natural alkaloid obtained from the dried leaves and stems of Nicotiana tabacum and Nicotiana rustica, where it occurs in concentrations of 0.5-8%. Cigarette tobacco varies in its nicotine content, but common blends contain 15-25 mg per cigarette, with a current trend towards levels.
Nicotine is a liquid alkaloid. It is water soluble and has a pKa of 8.5. It is a bitter-tasting liquid which is strongly alkaline in reaction and forms salts with acids. Nicotine should be stored at room temperature, below 86 F (30°C). Protect from the substance from light and air.
Nicotine may be consumed in several forms. Transdermal patches deliver 5 to 30 mg nicotine over 24 hours; used patch has significant nicotine content. Cigarette tobacco varies in its nicotine content but common blends contain 15 to 25 mg per cigarette with a current trend towards lower levels. Tobacco has been used in enemas and poultices (Gosselin, 1988). Nicotine insecticides have 40% solution of the sulfate. In nicotine polacrilex, 2 and 4 mg nicotine is bound to an ion exchange resin in a sugar-free flavored chewing gum base.
Kinetics of Nicotine
Nicotine enters the human body through several routes.
- Oral poisoning occurs in children who ingest cigarettes or cigars or nicotine gum. In adults chewing tobacco or nicotine gum, and people who ingest liquid nicotine in the form of insecticide preparations.
- Inhalation is the most frequent route of entry because of worldwide tobacco smoking.
- Dermal exposure to nicotine can lead to intoxication. Such exposure has been reported after spilling or applying nicotine-containing insecticides on the skin or clothes (Loockhart, 1933; Benowitz, 1987), and as a consequence of occupational contact with tobacco leaves (green tobacco sickness) (Weizenecker, 1970; Gehlbach, 1974).
Nicotine Absorption by Route of Exposure
Nicotine is a water and lipid soluble drug. When tobacco smoke reaches the small airways and alveoli of the lung, the nicotine is rapidly absorbed. The rapid absorption of nicotine from cigarette smoke through the lungs occurs because of the huge surface area of the alveoli and small airways, and because of dissolution of nicotine at physiological pH (approximately 7.4) which facilitates transfer across cell membranes.
Chewing tobacco, snuff, and nicotine polacrilex gum are of alkaline pH as a result of the selection of appropriate tobacco and/or buffering with additives by the manufacturers. The alkaline pH facilitates absorption of nicotine mucous membranes.
Nicotine inhaled in tobacco smoke enters the blood almost as rapidly as after rapid I.V. injections. Because of delivery into the lung, peak nicotine levels may be higher and lag time between smoking and entry into the brain shorter than after IV injection.
After smoking, the action of nicotine on the brain is expected to occur quickly. Rapid onset of effects after a puff is believed to provide optimal reinforcement for the development of drug dependence. The effect of nicotine declines as it is distributed to other tissues.
Apparent acute tolerance to nicotine, determined on the basis of observations of the relationship between venous blood levels and effects, may be due to distribution disequilibrium between venous and arterial blood; venous blood levels substantially underestimate concentrations of nicotine in arterial blood and at potential sites of action. True tolerance does, however, develop rapidly, with a half-life of development and regression of about 35 minutes. The kinetics of tolerance may be another determinant of cigarette smoking particularly when the smoker smokes his next cigarette.
Nicotine is a tertiary amine which is composed of a pyridine and a pyrrolidine ring. Nicotine undergoes a large first pass effect during which the liver metabolizes 80% to 90%; to a smaller extent, the lung also is able to metabolize nicotine.
The major metabolite of nicotine is cotinine. Cotinine levels in various biological fluids are widely used to estimate intake of nicotine in tobacco users. The usefulness of cotinine as a quantitative marker of nicotine intake, is limited by individual variability in percentage conversion of nicotine to cotinine and in the rate of elimination of cotinine itself.
Elimination by Route of Exposure
Nicotine and its metabolites (cotinine and nicotine 1-N-oxide) are excreted in the urine. At a pH of 5.5 or less, 23% is excreted unchanged. At a pH of 8, only 2% is excreted in the urine. The effect of urinary pH on total clearance is due entirely to changes in renal clearance. (Ellenhorn, 1988).
Nicotine is secreted into saliva. Passage of saliva containing nicotine into the stomach, combined with the trapping of nicotine in the acidic gastric fluid and reabsorption from the small bowel, provides a potential route for enteric nicotine recirculation. This recirculation may account for some of the oscillations in the terminal decline phase of nicotine blood levels after I.V. nicotine infusion or cessation of smoking.
Nicotine freely crosses the placenta and has been found in amniotic fluid and the umbilical cord blood of neonates. Nicotine is found in breast milk and the breast fluid of non-lactating women and in cervical mucous secretions (US Department of Health and Human Services, a report of the Surgeon General 1988).
Toxicology of Nicotine
Nicotine is an agonist at nicotinic receptors in the peripheral and central nervous system. In man, as in animals, nicotine has been shown to produce both behavioral stimulation and depression. Pharmacodynamic studies indicate a complex dose response relationship, due both to the complexity of intrinsic pharmacological actions and to rapid development of tolerance.
Human data shows that nicotine toxicity in adults and children are incomparable. For adults, the mean lethal dose has been estimated to be 30 to 60 mg (0.5-1.0 mg/kg) (Gosselin, 1988). For children, the lethal dose is considered to be about 10 mg of nicotine (Arena, 1974).
Carcinogenicity of Nicotine
Literature reports indicate that nicotine is neither an initiator nor a promoter of tumors in mice. There is inconclusive evidence to suggest that cotinine, an oxidized metabolite of nicotine, may be carcinogenic in the rat. (PDR, 1987).
Nicotine rapidly crosses the placenta and enters the fetus. Some investigations have reported teratogenic effects of high doses of nicotine, which interfered with steogenesis in mice and chick embryos. Chronic nicotine treatments of pregnant rats throughout gestation produced subtle neurological changes which manifested themselves as behavioral or electrophysiological alterations in the offspring. Thus, several studies suggest that nicotine, at least in high doses, may have toxic effects on the fetus. Smoking is associated with impaired growth and development of the fetus. Whether cigarette smoking is associated with increased rates of congenital; malformations in humans is controversial. Several studies show no association or a lower incidence of malformations in offspring of smoking mothers, but other reports positive associations. One study has reported an association between paternal smoking and the incidence of congenital malformations (US Department of Health and Human Services (1988)).
Smoking increases the metabolism of certain compounds and lowers blood levels of drug such as phenacetin, caffeine, theophylline, imipramine and pentazocine through enzyme induction. Other reported effects of smoking, which do not involve enzyme induction, include reduced diuretic effects of furosemide and decreased cardiac output, and antagonism of the hypotensive effects of propranolol, which may also relate to the normal effects of nicotine. Both smoking and nicotine can increase the level of circulating cortisol and catecholamines. Therapy with adrenergic agonists or with adrenergic blockers may need to be adjusted according to changes in smoking status.
Acute Poisoning from Nicotine
- Acute Poisoning through Ingestion
Symptoms of nicotine poisoning may develop within 15 minutes. The onset of symptoms is much more rapid after the ingestion of liquid nicotine (e.g. insecticide preparations) Death may occur within 5 minutes of ingestion of concentrated nicotine insecticides. Four to eight milligrams orally may produce serious symptoms in individuals not habituated to nicotine. Gastrointestinal signs and symptoms occur first and include mouth and throat burning followed by profuse salivation, nausea, vomiting, abdominal pain and occasionally diarrhea.
More severe intoxication results in dizziness, weakness and confusion, progressing to convulsions, hypertension and coma. Intense vagal stimulation may cause transient cardiac standstill or paroxysmal atrial fibrillation. Death is usually due to paralysis of respiratory muscles and/or central respiratory failure.
- Acute Poisoning through Inhalation
In humans, acute exposure to nicotine even in low doses (similar to the amounts consumed by tobacco users) elicits autonomic and somatic reflex effects. Dizziness, nausea and/or vomiting are commonly experienced by nonsmokers after low doses of nicotine, such as when people try their first cigarette. However, cigarette smokers rapidly become tolerant to these effects.
- Acute Poisoning Through Skin Exposure
Dermal exposure to nicotine can also lead to intoxication. Such exposures have been reported after spilling or applying nicotine containing insecticides on the skin or clothes and as consequence of occupational contact with tobacco leaves.
A self-limiting illness known as "green-tobacco sickness" has been described in young man handling uncured tobacco leaves in the field; it consists of pallor, vomiting and prostration and is probably due to the percutaneous absorption of nicotine from wet leaves.
Serious poisoning has occurred from the use of aqueous infusions of tobacco as enemas (Gosselin, 1988). Nicotine 2 mg administered intranasally as a 2% aqueous thickened solution was better absorbed than the same dose given as a chewing gum (Russell, 1983)
Chronic Poisoning from Nicotine
- Chronic poisoning through ingestion - This is possible by chewing tobacco or nicotine gums.
- Chronic poisoning through inhalation - Smoking causes coronary and peripheral vascular disease, cancer, chronic obstructive lung disease, peptic ulcer and reproductive disturbances, including prematurity.
Nicotine may contribute to tobacco related diseases, but direct causation has not been determined because nicotine is taken up simultaneously with a multitude of other potentially harmful substances that occur in tobacco smoke and smokeless tobacco.
- Chronic Poisoning through Skin Exposure - This happens through transdermal nicotine.
Nicotine May Cause Death
In fatal cases of nicotine poisoning, death is usually rapid; it occurs nearly always within one hour and occasionally within 5 minutes. According to the traditional view, death is due to paralysis of the respiratory muscles; paralysis of medullary centers controlling respiration requires a larger dose.
Circulatory failure is not necessarily permanent; if heart action can be initiated by external cardiac massage or intracardiac epinephrine while respiration is maintained, death may be prevented (Franke, 1936). If the patient survives the initial period, the prognosis is good (Gosselin 1988)
The overall effect on the cardiovascular system leads to tachycardia, peripheral vasoconstriction and elevations of blood pressure with an attendant increase in the work of the heart. Nicotine may induce vasospasm and cardiac arrhythmias. Tolerance does not develop to the catecholamine-releasing effects of nicotine.
Nicotine could contribute both to the atherosclerotic process and to acute coronary events by several mechanisms. Nicotine could promote atherosclerotic disease by its actions on lipid metabolism and coagulation by hemodynamic effects and/or by causing endothelial injury.
Based on its pharmacological actions, it is likely that nicotine plays a role in causing or aggravating acute coronary events. Myocardial infarction can be due to one or more of these precipitating factors: excessive demand for oxygen and substrates; thrombosis; and coronary spasm. Nicotine increases heart rate and blood pressure and, therefore, myocardial oxygen consumption.
In addition to creating an imbalance between myocardial oxygen supply and demand, nicotine may promote thrombosis. Nicotine may also induce coronary spasm by sympathetic activation or inhibition of prostacyclin. Coronary spasm has been observed during cigarette smoking (Maouad, 1984).
Sudden cardiac death in smokers might result from ischaemia, combined with the arrhythmogenic effects of increased amounts of circulating catecholamines released
by nicotine. Initial tachypnoea, but later dyspnoea, decreased respiratory rate, and cyanosis may be seen. Respiratory arrest may occur within minutes, and resultant death within one hour.
Chronic Effects of Nicotine
Nicotine may directly or indirectly influence the development of emphysema in smokers, but further research is needed to define the magnitude of the contribution of nicotine to the pathogenesis of smoking including chronic lung disease. Nicotine can also worsen pulmonary function in smokers who already have lung disease. Acute exposure to nicotine induces constriction of both central and peripheral airways (Yamatake, 1978).
The magnitude of bronchoconstriction observed in experimental animals and humans following acute inhalation of cigarette smoke is correlated with the level of nicotine in the smoke (Beck, 1986) suggesting that nicotine may be an important factor in the increased airways resistance of smokers.
The effects of nicotine are generally dose-dependent and extremely high doses can produce toxic symptoms such as delirium. These effects also occur in nicotine tolerant individuals. Nicotine first stimulates and later depresses the CNS. Headache, confusion, dizziness, agitation, restlessness and incoordination develop initially after serious nicotine overdose; 30 minutes later, convulsions and coma occur.
Neuromuscular symptoms include hypotonia, decreased deep tendon reflexes, weakness, fasciculations and paralysis of muscles (including respiratory muscles). Cholinergic symptoms often observed initially include diaphoresis, salivation, lacrimation, increased bronchial secretions, miosis and later mydriasis.
Nicotine has actions at the sympathetic ganglia and on the chemoreceptors of the aorta and carotid bodies. Nicotine also affects the adrenal medulla, releasing catecholamines.
Weakness, fasciculations and paralysis of muscles (including respiratory muscles) is observed.
Gastrointestinal symptoms occur first and include burning of the mouth and throat followed by profuse salivation, nausea, vomiting, abdominal pain and occasionally diarrhoea.
Cigarette smoking is a risk factor for peptic ulcer disease and an even stronger risk factor for delayed healing, failure to respond to therapy and relapse (Kikendall, 1984). In animals, nicotine potentiates peptic ulcer formation induced by histamine or pentagastrin (Konturek, 1971).
Nicotine may act by releasing free fatty acids, enhancing the conversion of VLDL (very low-density lipoproteins) to LDL (low density lipoproteins), impairing the clearance of LDL and/or by accelerating the metabolism of HDL. (Brischetto, 1983; Gluette Brown, 1986; Grasso, 1986; Hojnacki, 1986).
Pregnancy Risks Linked to Nicotine Use
Nicotine in any form may be harmful to the fetus. Exposure to nicotine during the last trimester has been associated with a decrease in breathing movements. These effects may be the result of decreased placental perfusion caused by nicotine. One miscarriage during nicotine therapy has been reported. Studies of pregnant rhesus monkeys have shown that maternal nicotine administration produced acidosis, hypoxia and hypercarbia in the fetus.
Nicotine has been shown to be teratogenic in mice treated cutaneously with 25 mg/kg, which is approximately 300 times the human oral dose. Studies in rats and monkeys have not demonstrated a teratogenic effect of nicotine in newborn which occur during cigarette smoking. Cigarette smoking is associated with impaired fetal growth and development.
Nicotine and Breastfeeding
Nicotine passes freely into the breast milk in small quantities, which are not clinically significant, averaging 91ppb in one study. Heavy smoking (20-30 cigarettes per day) may alter the supply of milk and cause nausea and vomiting in the infant.
The need for oral gratification and other psychological problems may result in the production of symptoms of withdrawal including anxiety, impaired concentration and memory, depression, hostility, sleep disturbances, and increased appetite (Ellenhorn 1988).
Managing Nicotine Reactions
There is no known antidote to counter adverse nicotine reactions. Immediate establishment of an airway, monitoring of breathing patterns, and maintenance of circulation are essential in serious overdose cases. Preparations for possible seizures of rapid progressing to coma must be initiated in serious overdose cases by establishment of an intravenous line, supplemental oxygen, cardiac monitoring, and direct observation.
Artificial ventilation procedures should be kept ready; oxygen may be required. Relevant laboratory analyses and other investigations include sample collection of plasma, biomedical analysis of full blood count and urinalysis (glycosuria), and toxicological analysis of plasma nicotine levels and metabolites in urine. Life supportive procedures and symptomatic treatment include artificial ventilation and oxygen therapy until spontaneous breathing is adequate. These procedures keep the airways clear.
Profuse salivation may require continuous oral suction. Bronchial secretions, excess salivation, and diarrhea may be ameliorated by atropine. If severe or persistent convulsions occur, they may be controlled with small intravenous doses of barbiturates or diazepam.
If contact was with the skin, remove contaminated clothing and wash the skin thoroughly with water without rubbing (avoid warm water). If the patient has swallowed nicotine, induce emesis if there are no convulsions and respiration is normal. Wash out the stomach. Activated charcoal may be left in the stomach.
Children who ingest more than one cigarette should receive activated charcoal and medical observation for at least several hours.
Haemodialysis and hemoperfusion have not been evaluated in acute nicotine poisoning. Acidification of urine may increase excretion of nicotine but although pharmacologically sound, its clinical value remains to be established and could be harmful.
Case reports from literature Malizia (1983) described four children who ingested two cigarettes each and developed salivation, vomiting, diarrhoea, tachypnoea, tachycardia, and hypotension within 30 minutes and depressed respiration and cardiac arrhythmias within 40 minutes. Convulsions occurred within 60 minutes of ingestion. All recovered after gastric lavage, activated charcoal, intermittent positive pressure ventilation, and 5 mg diazepam intravenously for convulsions.
A 23-year-old woman who had smoked two packs per day for several years chewed a single piece of nicotine gum (2 mg nicotine) after which she developed nausea, tremor, flushing, palpitations, paresthesias, pruritus, vomiting, diarrhoea, confusion and abdominal pain. She recovered after treatment and with prochlorperazine, morphine and atropine (Mensch, 1984).
Preventative measures for occupational exposure to nicotine include adequate ventilation, chemical goggles, mechanical filter respirator, rubber gloves, aprons and boots.