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Nicotine remains one of the most addictive and potent substances, regardless of whether it is delivered through a combustible cigarette, electronic cigarette, vape pen, hookah pipe or cigar

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Tolerance (neuroadaptation) is commonly attributed to the downregulation of nicotinic receptors in a compensatory response to overactivation to maintain homeostasis

In Eurasia, cannabis was common before the arrival of tobacco, and is known to have been used since at least 5000 BC