Im also heavily involved in Veneficium. Balance and understanding of this topic is important.
I do not have experience with ayahuasca, but my understanding from my voracious study is that its constituents vary, because it is a “brew,” and different tribes have different constituents. Even the poisonous Brugmansia can be incorporated (rarely).
For me, i do not simply engage with a substance one way or another and expect to just set off.
I create a ritualized context, as well as intentions when using a material which causes an altered state. I have not needed an external human “guide.” I guide myself and open myself to the guides through ritual, prayers to deities, and honoring the “spirit of the substance.” i have also reshaped my worldview to view them as sacred, distinct beings with magical powers.
For amanita muscaria, i have a special song between myself and the mushroom i sing, i perform actions to honor it as ive learned, and go forth about accomplishing what i need. And I only occasionally go full bore with Amanita Muscaria. My daily is microdose, and among my daily “magical substance use”, thats the only one that could be considered psychoactive, but microdosing is not supposed to be taking a psychoactive dose, and it really helps create a beautiful relationship and acts as a lovely aid in a variety of ways, medicinal and magical. I have not microdosed with psylocibes (only psychoactive dosing), but supposedly it has its own unique virtues from Amanita Muscaria that it can teach and strengthen also.
I utilize similar methods when working with baneful plants such as mandrake, datura and henbane - and then even the not baneful chemical LSD. Just because it is synthetic, does not mean it cannot be contextualized and act as an aid, but i dont consider its “spirit” the same way as natural entheogens. It hasnt revealed to me as a unique entity yet.
Whats important with these things with magical work or achieving “spiritual, altered states,” is creating a context for them to act in, and i like to create a timeframe as well, normally based on the amount of time the contents are supposed to act. This can be candles (i have not started any fires - i always light them on my shrines ensuring absolute space between the flames and anything flammable well before effect sets in and again, focus my intention that said candle is a timer for my experiences but i stay the fuck away from messing with fire always while in the throes) - but non flammable could be something like an hourglass or even a phone timer!
I do also think reliance on these things can short oneself. they are aids - and in my practice, i experience and consider the uniqueness of their spirit. They should not be discounted entirely or poo poo’d for the lack of control, though it is true you dont have the same control of a “sober mind”, you have different control, and in the swirling chaos of their power, you can seek to know them and flow with them. Depending on what is taken, it can be the strength of a riptide - so swim with the current, but create a context and intention to set where the current is heading while preparing to embark, whether thats popping caps, taking a tincture, smearing ointments, etc. Call to your guides. Call to the spirit of the aid. Set the stage and ambience, a clean, safe space, symbols of where you want to go, magical tools (non-flammable), statues of gods/goddesses if you work with or worship, beautiful music/representative of the journey you think you want to take, delicious scents, (safe) mood lighting.
Working with substance magically shouldnt be about the chemicals themselves - if their magic is only the chemicals… well then just study the chemistry. Thats why some people only work with them as “flower essences,” because theyre bigger than their chemicals.
I have ritualized my processes from the moment of harvest, the phases of the moon, to the implements used, to the words i say. These majestic and glorious entities were utilized well before we understood chemical constituents, and I have been led by my experiences to believe there is more there than just chemistry. Are they sacred because we as humans believe they are? Or are they sacred unto themselves? I asked those questions when i started gardening sacred plants only two years ago, and the answers i received… like i said, i reshaped my worldview!
Do your own thorough research. Be cautious. Pace yourself. Vet sellers as much as possible if purchasing. Grow or expose yourself to the living thing if possible, and even leave offerings to it if you can. If wildharvesting be absolutely cautious and ensure you are able to correctly identify a plant or fungus, because misidentification can have lethal consequences. As can working with baneful plants. Construct the context and provide a loose framework for the experience beforehand.
With Veneficium or working with these aids, I think it is most important that you be a seeker - that your lust for knowledge results in heavy study as well as cautious, practical, well-informed application until you find your equilibrium - if you find a teacher (avoid the big EGOs) thats great, ask so many questions: smart questions, foolish questions, better to ask something stupid than be dead.
I consider myself ever a student of these beauties (plants specifically but am currently studying fungi also, hence my preparations of amanita muscaria - and am ambitious to venture into medicinal fungal cultivation), they my teachers and companions. I mother and honor their physical forms, and they have not let me down yet. They are my allies, and have manifested true and beautiful things in their reality and mine.
TL;DR, I know. Find the wisdom for yourself. Or not.