Student Handout

What do nicotine, caffeine, cocaine, morphine, THC (tetrahydrocannibinol, the active ingredient in marijuana) and salicylate have in common? They all come from plants! The chemicals found in plants can have medicinal and non-medicinal uses. For example, the bark of the willow tree contains salicylate, the precursor to aspirin, and the foxglove plant makes digoxin, which is used to treat heart arrhythmias. The non-medicinal use of drugs such as nicotine, caffeine, cocaine, etc. stems from their ability to make a person “feel good”. These drugs have psychoactive effects in the brain, although they can also have non-psychoactive effects in other parts of the body as well.

1. Provide the name of the plants that contain the following drugs: nicotine, cocaine, morphine, THC and salicylate.

2. What is a psychoactive property?

3. Why would plants make compounds that have psychoactive properties?

The characteristics of the chemicals found in plants have an important impact in how they are handled by the body. One of the most common forms of active compounds contained in plants is called alkaloids. Nicotine, caffeine, cocaine and morphine are all alkaloids. Alkaloids are synthesized in a plant cell and then stored in vacuoles. In contrast, compounds like THC are not alkaloids; instead they are more like oils.

4. What is an alkaloid? Describe the typical characteristics of its chemical structure.

5. What aspect of the chemical structure of THC gives it its oily character?

6. In what kind of plants are alkaloids found? Where in the plant are alkaloids found?

7. Describe the structure of a vacuole. What does it do inside the cell?

In order to be consumed by humans, the drugs contained in plants need to be released from the plant cells. For medicinal or non-medicinal use, drugs are often extracted chemically. But in the case of non-medicinal use, drugs are also obtained by smoking the plant (e.g., tobacco, marijuana, opium) (see Module 1), smoking the extracted compound (e.g., crack cocaine), or chewing the dried leaves (e.g. chewing tobacco or coca leaves). The extraction of drugs, especially alkaloids, from plants is based on their chemical properties (acid-base characteristics) and their solubility in water versus an organic solvent.

8. In what form, charged or uncharged, does an alkaloid exist in the plant? (Hint: if it’s in a vacuole, it’s dissolved in water).

9. To chemically extract a drug from the plant, it must be in its non-polar (uncharged) form. Would one add an acid or a base to do this? Draw an equilibrium reaction of an alkaloid such as morphine in an acidic and in a basic medium. What is involved in the extraction process?

10. If a plant is smoked to release a drug, more drug will be volatilized in the smoke if the drug is in its non-polar form. In fact, tobacco companies play a “chemical trick” to increase the nicotine in the smoke by keeping the nicotine in the cigarette in its non-polar form. What do the tobacco companies add to the tobacco to do this? Why does this work? How does this help the tobacco companies to sell more cigarettes?

Once these drugs get into the body, they travel through the bloodstream and they are delivered to tissues, including the brain. To produce their effects, drugs like nicotine, morphine, cocaine, caffeine, and even aspirin bind to specific proteins located on cell membranes or inside cells. These proteins include enzymes, receptors, and transporters.

11. Why would the body have protein targets for drugs that are found in plants?

12. What is an enzyme? What is a receptor? What is a transporter? Indicate which of these proteins is a target for nicotine, cocaine, morphine, caffeine, THC and aspirin.

The binding of the drug to the protein involves several types of forces, including electrostatic forces, hydrogen bonds, and van der Waals forces. There are a few examples of covalent interactions between a drug and its target, but this is rare. One example is nerve gas (see Module 4).

13. How do electrostatic forces, hydrogen bonds and van der Waals forces help the drug to bind to the protein? When the drug molecule approaches the protein, which force occurs first? Which force contributes most to the stability of the interaction?

14. Why is it uncommon to find drugs that interact with proteins in a covalent manner?

When the drug binds to the protein target, it causes a change in the shape (“conformation”) of the protein. This usually causes something to happen in the cell that then leads to the actual biological response.

15. The conformation of the receptor for nicotine changes when nicotine binds to it. What happens next? What is the biological response that is produced?

The last question is a bit tricky. The biological response that is produced will depend on where in the body the receptors for nicotine are found. Receptors for nicotine (also called acetylcholine receptors because acetylcholine, found in the body, binds to them) are found on neurons in many parts of the brain and on muscle cells (also see Module 4). In neurons, nicotine causes electrical impulses to be generated, causing release of neurotransmitters from neuron terminals. In muscles, nicotine causes contraction of the muscle.

16. Where are the protein targets for cocaine found? List 3 biological responses produced by cocaine, depending on where it binds to its target.

17. Where are the protein targets for aspirin found? List 3 biological responses produced by aspirin in three areas of the body.