The first time you use an entheogen will be the most formative and will set the tone for rest of your relationship together. This first time has the potential to be a complex dance between your will and the power of the spirit; the spirit may have conditions for you to agree to if you wish to continue using its plant children and you will have to decide if those conditions are reasonable. While the spirits will hold back a measure of the plant's poison once an understanding has been reached, this allowance should not be mistaken for anything except permission for you to enter their territory and work with their power. IN NO WAY does this make a plant safer to use; you're still playing with poison. The poison is there to remind us that we are not the one in control of the trance that we work together with the spirit to create. The first time I drank datura tea, Queen Toloache let me enjoy a fever that took all night to break; it wasn't life threatening by a long shot, but it was enough to drive home just how much I was at her mercy and won an even greater degree of respect from me forever afterwards. Entheogens also aren't the tastiest plants around; the bitterness is another reminder that this work has the potential to take us far outside our personal comfort zone, and the willingness to accept the bitterness of the herb is a form of sacrifice for the knowledge gained.
Personally, I like setting aside the first session with a new plant to just get to know it; how my body will react, how my mind will react, and exactly how the spiritual powers work after the chemical effects have taken hold are important considerations that I don't want to be unprepared for when the time comes to use a plant for a particular task. Needless to say, this experimentation is vastly different than the experimentation done by casual users; it would be more accurate to call this education rather than experimentation. These purely educational sessions don't end after the first time; I think I've spent more plant trance sessions learning from them then I have spent doing anything else. Again, this will vary from person to person and from herb to herb; some plant spirits have a great deal to say and desire your undivided attention while they speak, others give you some basic information and then step back.
Part of why being experienced in trance states is so important on this path is that you aren't in direct control of the altered state you enter with the help of a plant. You control when you take the dose, but past that, you're largely at the whim of the spirit (or dependant on whatever assistance medical science can deliver). Some of these plants naturally create emotional states that have to be dealt with as they arise without allowing them to take over; fear, anxiety, or lassitude are just part of a plant's powers. Those feelings need to be accepted and set aside as they arise, or they may become overwhelming and halt your progress. Many herbs have the ability to call forward hidden emotions that have been tucked behind the front we use to face the world. A person's attitude and emotional state are important factors when engaging in entheogenic work, and it's no wonder that many cultures have prescribed routines that need followed before engaging in a plant-induced trance. Practices such as fasting, abstaining from sex, periods of meditation and seclusion, and withdrawing from normal activities help create a mind that is clear from distraction and a body that is open to the full biological effects of an herb. How necessary these practices are will vary from person to person and will depend on the plant they're working with. Even if you don't use these techniques every time you engage in plant work, some experience with them will give you valuable tools.
Knowing how to recover from an entheogenic trance is just as important as knowing how to go into one. This is often very draining work; the body must assimilate unfamiliar material and the mind has been stretched in new ways. It takes me about 24-48 hours before I begin to feel like myself again; until then I'm usually drained and may be a little addle-brained, though some herbs have little lasting effect after the trance has ended. When done correctly and in accordance with Right Action, the after-effects of an entheogenic trance are healing and peaceful, even considering physical and mental fatigue. What can kill can also cure; the trance state induced by several plants are similar to deep healing sleep and will leave a person feeling renewed. Ideally, you will be able to take the time to enjoy the recovery; it's a very sacred time and deserves to be savored.